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class="bkr_bib"><h1 id="_NBK576823_"><span itemprop="name">Evidence reviews for endocrine therapy for invasive disease</span></h1><div class="subtitle">Early and locally advanced breast cancer: diagnosis and management</div><p><b>Evidence review D</b></p><p><i>NICE Guideline, No. 101</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Alliance (UK)</span>.</p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2018 Jul</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3008-1</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2018.</div></div><div class="bkr_clear"></div></div><div id="chd.s1"><h2 id="_chd_s1_">Endocrine therapy for invasive disease</h2><p>This evidence report contains information on 3 reviews relating to endocrine therapy for invasive disease.</p><ul id="l559"><li id="lt1471" class="half_rhythm"><div><a href="#chd.s1.1">Review question 4.1</a> What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</div></li><li id="lt1472" class="half_rhythm"><div><a href="#chd.s1.2">Review question 4.2</a> What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</div></li><li id="lt1473" class="half_rhythm"><div><a href="#chd.s1.3">Review question 10.4</a> What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</div></li></ul><div id="chd.s1.1"><h3>Review question 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h3><div id="chd.s1.1.1"><h4>Introduction</h4><p>Treatment of women with oestrogen receptor-positive (ER-positive) early stage invasive breast cancer with adjuvant endocrine therapy for 5 years reduces recurrence rates in ER-positive breast cancer by about half and breast cancer mortality by about a third.</p><p>Tamoxifen, a selective oestrogen receptor modulator is effective in premenopausal or postmenopausal women and can therefore be used regardless of the menopausal status of the patient. Aromatase inhibitors reduce the non-ovarian production of oestrogen and can be used in postmenopausal women to greatly reduce systemic oestrogen levels and thus to avoid stimulation of ER-positive breast cancer.</p><p>Unlike most cancers, the risk of relapse for ER-positive invasive breast cancer remains significant even after completing 5 years of endocrine therapy. The aim of this review is to identify the optimal duration of endocrine therapy to minimise the risk of disease recurrence in women with ER-positive breast cancer.</p></div><div id="chd.s1.1.2"><h4>PICO table</h4><p>See <a class="figpopup" href="/books/NBK576823/table/chd.tab1/?report=objectonly" target="object" rid-figpopup="figchdtab1" rid-ob="figobchdtab1">Table 1</a> for a summary of the population, intervention, comparison and outcome (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab1"><a href="/books/NBK576823/table/chd.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab1" rid-ob="figobchdtab1"><img class="small-thumb" src="/books/NBK576823/table/chd.tab1/?report=thumb" src-large="/books/NBK576823/table/chd.tab1/?report=previmg" alt="Table 1. Summary of the protocol (PICO table)." /></a><div class="icnblk_cntnt"><h4 id="chd.tab1"><a href="/books/NBK576823/table/chd.tab1/?report=objectonly" target="object" rid-ob="figobchdtab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For full details see review protocol in <a href="#chd.appa">appendix A</a>.</p></div><div id="chd.s1.1.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>; see the <a href="/books/n/niceng101erm/?report=reader" class="toc-item">methods</a> chapter for further information.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy.</p></div><div id="chd.s1.1.4"><h4>Clinical evidence</h4><div id="chd.s1.1.4.1"><h5>Included studies</h5><p>Ten studies (number of participants, N=22,221) were included in the review (<a class="bibr" href="#chd.s1.1.ref1" rid="chd.s1.1.ref1">Davies, 2013</a>; <a class="bibr" href="#chd.s1.1.ref3" rid="chd.s1.1.ref3">Fisher, 1996</a>; <a class="bibr" href="#chd.s1.1.ref4" rid="chd.s1.1.ref4">Fisher, 2001</a>; <a class="bibr" href="#chd.s1.1.ref5" rid="chd.s1.1.ref5">Goss, 2005</a>; <a class="bibr" href="#chd.s1.1.ref7" rid="chd.s1.1.ref7">Jakesz, 2007</a>; <a class="bibr" href="#chd.s1.1.ref8" rid="chd.s1.1.ref8">Mamounas, 2008</a>; <a class="bibr" href="#chd.s1.1.ref9" rid="chd.s1.1.ref9">Muss, 2008</a>; <a class="bibr" href="#chd.s1.1.ref11" rid="chd.s1.1.ref11">Stewart, 1996</a>; <a class="bibr" href="#chd.s1.1.ref12" rid="chd.s1.1.ref12">Stewart, 2001</a>; <a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey, 1996</a>), which report data from 7 trials: Austrian Breast and Colorectal Cancer Study Group (ABCSG) 6a (number of publications, k=1), Adjuvant Tamoxifen Longer Against Shorter (ATLAS; k=1), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 (k=2), NSABP B-33 (k=1), MA.17 trial (k=2), Scottish Adjuvant Tamoxifen Trial (k=2), and <a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey, 1996</a> (k=1).</p><p>Four trials compared tamoxifen taken for longer than 5 years with tamoxifen taken for 5 years only: the Scottish Adjuvant Tamoxifen Trial and <a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey (1996)</a> compared tamoxifen to be taken indefinitely/until relapse with 5 years of adjuvant tamoxifen; the ATLAS and B-14 trials both compared 10 years of tamoxifen with 5 years of tamoxifen (with the addition of 5 years of placebo following tamoxifen in B-14).</p><p>Three trials compared tamoxifen followed by an aromatase inhibitor with tamoxifen alone: MA.17 compared 5 years of tamoxifen followed by 5 years of letrozole against 5 years of tamoxifen followed by 5 years of placebo, B-33 compared 5 years of tamoxifen followed by 5 years of exemestane with 5 years of tamoxifen followed by 5 years of placebo, and ABCSG 6a compared 5 years of tamoxifen followed by anastrozole for 3 years with 5 years of tamoxifen only.</p><p>Only one study (<a class="bibr" href="#chd.s1.1.ref7" rid="chd.s1.1.ref7">Jakesz, 2007</a>) reported data for critical outcomes by any subgroups of interest; however, the only subgroup reported was individuals with grade 3 cancer. Due to significant heterogeneity and the critical nature of survival outcomes, unplanned subgroup analysis was conducted for disease-free and overall survival outcomes to investigate differences in estimated effects between those studies where tamoxifen was continued and those where individuals switched to an aromatase inhibitor.</p><p>The clinical studies included in this evidence review are summarised in <a class="figpopup" href="/books/NBK576823/table/chd.tab2/?report=objectonly" target="object" rid-figpopup="figchdtab2" rid-ob="figobchdtab2">Table 2</a> and evidence from these are summarised in the clinical GRADE evidence profile below (<a class="figpopup" href="/books/NBK576823/table/chd.tab3/?report=objectonly" target="object" rid-figpopup="figchdtab3" rid-ob="figobchdtab3">Table 3</a>). See also the study selection flow chart in <a href="#chd.appc">appendix C</a>, forest plots in <a href="#chd.appe">appendix E</a>, and study evidence tables in <a href="#chd.appd">appendix D</a>.</p></div><div id="chd.s1.1.4.2"><h5>Excluded studies</h5><p>Studies not included in this review with reasons for their exclusions are provided in <a href="#chd.appk">appendix K</a>.</p></div></div><div id="chd.s1.1.5"><h4>Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab2"><a href="/books/NBK576823/table/chd.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab2" rid-ob="figobchdtab2"><img class="small-thumb" src="/books/NBK576823/table/chd.tab2/?report=thumb" src-large="/books/NBK576823/table/chd.tab2/?report=previmg" alt="Table 2. Summary of included studies." /></a><div class="icnblk_cntnt"><h4 id="chd.tab2"><a href="/books/NBK576823/table/chd.tab2/?report=objectonly" target="object" rid-ob="figobchdtab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. </p></div></div><p>See <a href="#chd.appd">appendix D</a> for full evidence tables.</p></div><div id="chd.s1.1.6"><h4>Quality assessment of clinical studies included in the evidence review</h4><p>The clinical evidence profile for this review question (duration of endocrine therapy) is presented in <a class="figpopup" href="/books/NBK576823/table/chd.tab3/?report=objectonly" target="object" rid-figpopup="figchdtab3" rid-ob="figobchdtab3">Table 3</a>. The quality of evidence ranges from very low to high. Main reasons for downgrading evidence include significant heterogeneity and imprecision around the estimates due to a small number of events of interest and wide confidence intervals.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab3"><a href="/books/NBK576823/table/chd.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab3" rid-ob="figobchdtab3"><img class="small-thumb" src="/books/NBK576823/table/chd.tab3/?report=thumb" src-large="/books/NBK576823/table/chd.tab3/?report=previmg" alt="Table 3. Summary clinical evidence profile: Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only." /></a><div class="icnblk_cntnt"><h4 id="chd.tab3"><a href="/books/NBK576823/table/chd.tab3/?report=objectonly" target="object" rid-ob="figobchdtab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Summary clinical evidence profile: Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only. </p></div></div><p>See <a href="#chd.appf">appendix F</a> for full GRADE tables.</p></div><div id="chd.s1.1.7"><h4>Economic evidence</h4><div id="chd.s1.1.7.1"><h5>Included studies</h5><p>One relevant study was identified in a literature review of published cost-effectiveness analyses on this topic; <a class="bibr" href="#chd.s1.1.ref2" rid="chd.s1.1.ref2">Erman 2014</a> (see <a href="#chd.apph">appendix H</a> and <a href="#chd.appi">appendix I</a> for summary and full evidence tables). The study considered the cost-effectiveness of extended tamoxifen or extended aromatase inhibitors in comparison to standard tamoxifen. The analysis was a cost-utility analysis measuring effectiveness in terms of quality adjusted life years (QALYs).</p></div><div id="chd.s1.1.7.2"><h5>Excluded studies</h5><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economic literature search for the list of excluded studies.</p></div></div><div id="chd.s1.1.8"><h4>Summary of studies included in the economic evidence review</h4><p>The base case results of <a class="bibr" href="#chd.s1.1.ref2" rid="chd.s1.1.ref2">Erman 2014</a> showed that extended tamoxifen and extended aromatase inhibitors were both cost-effective in comparison to a standard tamoxifen regimen. Extended tamoxifen was found to be less costly and more effective than standard tamoxifen (i.e. dominant) while extended aromatase inhibitors were more effective and more costly but likely to be cost-effective with a very small ICER of $178 per QALY (CAD). Using dominance rank to determine the optimal strategy, it was found that extended aromatase inhibitors were more effective and more costly than extended tamoxifen with an ICER of $3,402 per QALY likely to be considered cost-effective.</p><p>Probabilistic sensitivity analysis showed that at a threshold of $50,000 per QALY (CAD), the probability of being cost-effective was 70% for extended aromatase inhibitors, 30% for extended tamoxifen and 0.003% for standard tamoxifen.</p><p>The analysis was deemed to be only partially applicable to the decision problem in the UK setting as it was conducted from the perspective of the Canadian health care system. Some potentially serious limitations were identified in the analysis including the absence of some potentially key input parameters from the sensitivity analysis (most notably utility weights).</p></div><div id="chd.s1.1.9"><h4>Evidence statements</h4><div id="chd.s1.1.9.1"><h5>Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only</h5><div id="chd.s1.1.9.1.1"><h5>Critical outcomes</h5><div id="chd.s1.1.9.1.1.1"><h5>Treatment-related morbidity</h5><ul id="l582"><li id="lt1527" class="half_rhythm"><div>There is very low quality evidence from 3 RCTs (N=7157) that there is no clinically important effect of duration of endocrine therapy on hot flushes at 2 month to 4 year follow-up.</div></li><li id="lt1528" class="half_rhythm"><div>There is high quality evidence from 4 RCTs (N=14581) that there is no clinically important effect of duration of endocrine therapy on any secondary cancer at 5.6 to 7.6 year follow-up.</div></li><li id="lt1529" class="half_rhythm"><div>There is high quality evidence from 3 RCTs (N=14388) that there is no clinically important effect of duration of endocrine therapy on contralateral breast cancer at 6 to 7.6 year follow-up.</div></li><li id="lt1530" class="half_rhythm"><div>There is moderate quality evidence from 3 RCTs (N=14388) that endocrine therapy for greater than 5 years produces clinically meaningful increases in endometrial cancer at 6 to 7.6 year follow-up relative to endocrine therapy for 5 years only.</div></li><li id="lt1531" class="half_rhythm"><div>There is moderate quality evidence from 4 RCTs (N=20438) that there is no clinically important effect of duration of endocrine therapy on bone fractures at 2 month to 7.6 year follow-up.</div></li><li id="lt1532" class="half_rhythm"><div>There is high quality evidence from 3 RCTs (N=7567) that there is no clinically important effect of duration of endocrine therapy on arthralgia at 2 month to 4 year follow-up.</div></li><li id="lt1533" class="half_rhythm"><div>There is high quality evidence from 3 RCTs (N=18876) that there is no clinically important effect of duration of endocrine therapy on cardiac disease/events at 2 month to 7.6 year follow-up.</div></li><li id="lt1534" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=5149) that there is no clinically important effect of duration of endocrine therapy on hypertension at 4 year follow-up.</div></li><li id="lt1535" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=5126) that endocrine therapy for greater than 5 years produces clinically meaningful increases in osteoporosis at 4 year follow-up relative to endocrine therapy for 5 years only.</div></li><li id="lt1536" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=5149) that there is no clinically important effect of duration of endocrine therapy on myalgia at 4 year follow-up.</div></li><li id="lt1537" class="half_rhythm"><div>There is low quality evidence from 2 RCTs (N=1755) that endocrine therapy for greater than 5 years produces clinically meaningful increases in grade 3+ toxicities at 2.5 to 5.6 year follow-up relative to endocrine therapy for 5 years only.</div></li><li id="lt1538" class="half_rhythm"><div>There is moderate quality evidence from 2 RCTs (N=6005) that endocrine therapy for greater than 5 years produces clinically meaningful increases in vaginal dryness at 2 month to 4 year follow-up relative to endocrine therapy for 5 years only. However, this was not statistically significant.</div></li><li id="lt1539" class="half_rhythm"><div>There is low quality evidence from 2 RCTs (N=6005) that there is no clinically important effect of duration of endocrine therapy on vaginal bleeding at 2 month to 4 year follow-up.</div></li><li id="lt1540" class="half_rhythm"><div>There is very low quality evidence from 2 RCTs (N=2008) that there is no clinically important effect of duration of endocrine therapy on vaginal discharge at 2 month to 4 year follow-up.</div></li><li id="lt1541" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=12894) that there is no clinically important effect of duration of endocrine therapy on stroke at 7.6 year follow-up.</div></li><li id="lt1542" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1152) that there is no clinically important effect of duration of endocrine therapy on irregular menstruation at 4 year follow-up.</div></li><li id="lt1543" class="half_rhythm"><div>There is moderate quality evidence from 3 RCTs (N=14902) that endocrine therapy for greater than 5 years produces clinically meaningful increases in phlebitis/thromboembolic events at 2 month to 7.6 year follow-up relative to endocrine therapy for 5 years only.</div></li></ul></div><div id="chd.s1.1.9.1.1.2"><h5>Disease-free survival</h5><ul id="l583"><li id="lt1544" class="half_rhythm"><div>There is evidence from 1 RCT (N=171) that there is no clinically important effect of duration of endocrine therapy on disease-free survival at 5 year follow-up for women with grade 3 tumours. It was not possible to judge imprecision, and therefore the quality of this evidence, as number of events were not reported.</div></li><li id="lt1545" class="half_rhythm"><div>There is low quality evidence from 4 RCTs (N=8480) that there is no clinically important effect of duration of endocrine therapy on disease-free survival at 5.6 to 15 year follow-up for women who continue tamoxifen.</div></li><li id="lt1546" class="half_rhythm"><div>There is high quality evidence from 3 RCTs (N=7575) that endocrine therapy for greater than 5 years produces clinically meaningful increases in disease-free survival compared with endocrine therapy for 5 years only at 2.5 to 5 year follow-up for women who switch from tamoxifen to an aromatase inhibitor after 5 years.</div></li></ul></div><div id="chd.s1.1.9.1.1.3"><h5>Overall survival</h5><ul id="l584"><li id="lt1547" class="half_rhythm"><div>There is moderate quality evidence from 4 RCTs (N=8533) that there is no clinically important effect of duration of endocrine therapy on overall survival at 5.6 to 15 year follow-up for women who continue tamoxifen.</div></li><li id="lt1548" class="half_rhythm"><div>There is moderate quality evidence from 2 RCTs (N=6022) that there is no clinically important effect of duration of endocrine therapy on overall survival at 4 to 5 year follow-up for women who switch from tamoxifen to an aromatase inhibitor after 5 years.</div></li></ul></div></div><div id="chd.s1.1.9.1.2"><h5>Important outcomes</h5><div id="chd.s1.1.9.1.2.1"><h5>Compliance/adherence</h5><ul id="l585"><li id="lt1549" class="half_rhythm"><div>There is low quality evidence from 4 RCTs (N=19558) that there is no clinically important effect of duration of endocrine therapy on compliance.</div></li></ul></div><div id="chd.s1.1.9.1.2.2"><h5>Treatment-related mortality</h5><ul id="l586"><li id="lt1550" class="half_rhythm"><div>No evidence was found for this outcome.</div></li></ul></div><div id="chd.s1.1.9.1.2.3"><h5>Health-related quality of life</h5><ul id="l587"><li id="lt1551" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=382) that there is no clinically important effect of duration of endocrine therapy on HRQoL as measured change from baseline by SF-36 physical and mental health scores at 2 year follow-up.</div></li><li id="lt1552" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=386) that there is no clinically important effect of duration of endocrine therapy on HRQoL as measured change from baseline by MENQOL vasomotor, psychosocial, physical and sexual scores at 2 year follow-up.</div></li></ul></div></div></div><div id="chd.s1.1.9.2"><h5>Economic evidence statement</h5><ul id="l588"><li id="lt1553" class="half_rhythm"><div>There is evidence from one cost-utility analysis showing that extended tamoxifen was dominant in comparison to standard tamoxifen, while extended aromatase inhibitors have an ICER of $178 per QALY in comparison to standard tamoxifen and an ICER of $3,402 per QALY in comparison to extended tamoxifen. The analysis was partially applicable with some potentially serious limitations.</div></li></ul></div></div><div id="chd.s1.1.10"><h4>The committee’s discussion of the evidence</h4><div id="chd.s1.1.10.1"><h5>Interpreting the evidence</h5><div id="chd.s1.1.10.1.1"><h5>The outcomes that matter most</h5><p>As this review question is related to the duration of therapy required to prevent disease recurrence, the committee identified disease-free survival and overall survival as critical outcomes. Treatment-related morbidities was also a critical outcome as extending treatment affords greater opportunity for side effects of treatment to occur, and the optimal duration may be a balance of effectiveness and potential side-effects. Compliance/adherence, treatment-related mortality and health-related quality of life were selected as important outcomes.</p><p>These outcomes are important to service users as increased survival is normally prioritised. However, the tolerability of, and adherence to, treatments will be affected by the severity of side effects and the impact these have on quality of life.</p><p>No evidence was identified for treatment-related mortality.</p></div><div id="chd.s1.1.10.1.2"><h5>The quality of the evidence</h5><p>The quality of the evidence for this review was assessed using GRADE. For disease-free survival the evidence was of a low quality for the mixed population and for those who continued tamoxifen due to large amount of heterogeneity. However, it was not possible to explore heterogeneity in the tamoxifen studies as the subgroups of interest to the committee were not reported in trials that contributed to this estimate. For disease-free survival in the population who switched to an aromatase inhibitor, the evidence was of high quality.</p><p>For overall survival the evidence was of moderate quality. There was serious inconsistency in the tamoxifen studies (but again this could not be explored due to a lack of evidence reported for the subgroups) and only a small number of events of interest were reported for the population who switched to an aromatase inhibitor.</p><p>The quality of evidence for treatment-related morbidity ranged from very low to high quality. The low quality was mainly due to uncertainty around the estimate due to small number of events of interest and wide confidence intervals</p><p>Compliance evidence was all low quality due to unexplained heterogeneity (and as the subgroups of interest were only identified by the committee for critical outcomes this heterogeneity could not be investigated). Finally, for health-related quality of life the evidence was of high quality.</p><p>Based on the high quality of the evidence relating to improvements in disease-free survival in those who switched to an aromatase inhibitor after 5 years of tamoxifen, the committee made a strong recommendation. It was recommended that aromatase inhibitors were offered to post-menopausal women following 2 to 5 years of tamoxifen, rather than the 5 year evidence shown in the current review, as the previous guideline CG80 (<a class="bibr" href="#chd.s1.1.ref10" rid="chd.s1.1.ref10">NICE 2009</a>) recommended an aromatase inhibitor was offered after 2–3 years of tamoxifen; this recommendation was retained (as the current review only examined >5 years of endocrine therapy compared with 5 years of treatment) and combined with the current recommendation for clarity. The low quality of evidence available for the tamoxifen studies meant that the committee were only able to make a weak recommendation here. There was also no evidence available that evaluated extended duration of treatment for those post-menopausal women who started endocrine therapy with an aromatase inhibitor. The committee were therefore unable to make a recommendation for this therapy option, but agreed that they did not need to make a research recommendation as there are already ongoing trials addressing issue.</p></div><div id="chd.s1.1.10.1.3"><h5>Benefits and harms</h5><p>The main benefit demonstrated by the evidence was an improved disease-free survival (an additional 3% of people were free from disease at 2.5 years when switched after 5 years from tamoxifen to an aromatase inhibitor).</p><p>However, the harms identified with the increased duration of endocrine therapy included increased rates of endometrial cancer, osteoporosis, grade 3 toxicities and phlebitis/thromboembolic events. The committee noted that some of these treatment-related morbidities were serious and may negate the beneficial effects of the additional duration of treatment, and that the additional duration of treatment may increase the likelihood of a patient experiencing any side-effect. However, the committee agreed that people prioritise survival over other outcomes, and that the evidence review had confirmed that extending treatment does not lead to a significant reduction in health-related quality of life.</p><p>Furthermore, the committee noted that the absolute differences in rates of side effects are small for the comparison between interventions, and that the numbers needed to harm (i.e. the number of people you would need to treat for one additional incidence of the side effect to occur, number need to harm, NNH) are large (based on moderate to high quality evidence). The NNH values are also lower than the number needed to treat (i.e. the number of people you would need to treat for one additional person to be free from disease at 2.5 years, NNT) as shown here:
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<ul id="l589"><li id="lt1554" class="half_rhythm"><div>NNT for disease-free survival in those switched to an aromatase inhibitor = 33</div></li><li id="lt1555" class="half_rhythm"><div>NNH for osteoporosis = 45</div></li><li id="lt1556" class="half_rhythm"><div>NNH for endometrial cancer = 125</div></li><li id="lt1557" class="half_rhythm"><div>NNH for phlebitis/thromboembolic events = 250</div></li></ul></p><p>Finally, the committee recognised that the recommendations may lead to over-treatment in low risk individuals. However, as the committee also made a recommendation to discuss the benefits and harms with individual person, this should also mitigate the risk of over-treatment in people where the harms may outweigh the benefits.</p></div></div><div id="chd.s1.1.10.2"><h5>Cost effectiveness and resource use</h5><p>One relevant study was identified in a literature review of published cost-effectiveness analyses on this topic; <a class="bibr" href="#chd.s1.1.ref2" rid="chd.s1.1.ref2">Erman 2014</a>. The study considered the cost-effectiveness of extended tamoxifen or extended aromatase inhibitors in comparison to standard tamoxifen. The study was conducted from the perspective of the Canadian health care system and was therefore only partially applicable to the UK NHS context.</p><p>The base case results showed that extended tamoxifen and extended aromatase inhibitors were both cost-effective in comparison to standard tamoxifen. Extended tamoxifen was found to be less costly and more effective than standard tamoxifen (i.e. dominant) while extended aromatase inhibitors were more effective and more costly but likely to be cost-effective with a very small ICER of $178 per QALY (CAD). Using dominance rank to determine the optimal strategy, it was found that extended aromatase inhibitors were more effective and more costly than extended tamoxifen with an ICER of $3,402 per QALY likely to be considered cost-effective. Probabilistic sensitivity analysis showed that at a threshold of $50,000 per QALY (CAD), the probability of being cost-effective was 70% for extended aromatase inhibitors, 30% for extended tamoxifen and 0.003% for standard tamoxifen.</p><p>While the analysis was not directly applicable, it does suggest that that extended aromatase inhibitors or tamoxifen are cost-effective in comparison to standard tamoxifen. While the magnitude of the costs may vary between countries, it is likely that the same effects would be observed. Therefore, the additional costs of tamoxifen or aromatase inhibitors are likely to be offset, at least partially offset by downstream cost savings, while the improvements in clinical effectiveness would translate into QALY gains. It then seems likely that the strategy would be cost-effective in cost per QALY terms.</p><p>The committee carefully considered the potential resource impact in this topic area as they were aware of the large number of women that are likely to be affected by the recommendations. However, while the population affected may be large, the cost of interventions are very low. The cost of aromatase inhibitors and tamoxifen were estimated based on prices reported in the electronic market information tool (eMit). Letrozole 2.5mg was reported to cost £1.52 for a pack of 28, anastrozole 1mg was reported to cost £0.74 for a pack of 28, exemestane 25mg was reported to cost £4.16 for a pack of 30 and tamoxifen 20mg was reported to cost £1.44 for a pack of 30. This equates to an estimated cost per dose of £0.05, £0.03, £0.14 and £0.05 for letrozole, anastrozole, exemestane and tamoxifen, respectively. The committee discussed whether the extended treatment might require additional consultations but this was thought unlikely as consultations tend to occur frequently when treatment is commenced but stop after a few years of treatment. However, it is possible that there may be an additional consultation to review medications at 5 years.</p><p>The committee commented that the recommendations reflect current practice for some centres as some women already receive extended treatment. Therefore the overall cost impact of implementing the recommendation nationwide will be smaller and any cost increases associated with continued medication will vary based on current local protocols.</p><p>Overall, when taking all factors into account, it was thought that the recommendations were likely to be cost-effective and unlikely to have a substantial resource impact of more than £1 million per year.</p></div><div id="chd.s1.1.10.3"><h5>Other factors the committee took into account</h5><p>The committee questioned the relevance of the Scottish adjuvant tamoxifen trial and NSABP-14 trial as these were older trials in which people received treatment during the 1980s. However, no specific information in the publications was identified that was inconsistent with current practice so a sensitivity analysis was not performed to evaluate the inclusion of these trials.</p><p>The committee agreed that the ATLAS and Adjuvant Tamoxifen Treatment Offers More? (aTTom) trials are likely to be consistent with current standards. Evidence from ATLAS included in the current review showed a benefit in terms of disease-free survival (82% vs. 79%) and overall survival (81% vs. 79%) for individuals who continued tamoxifen to 10 years compared with those that took it for 5 years. It was not possible to include the results of the aTTom trial in the evidence review as they are only available in abstract form (<a class="bibr" href="#chd.s1.1.ref1" rid="chd.s1.1.ref1">Gray, 2013</a>) with insufficient evidence to calculate hazard ratios. The results, however, are consistent with ATLAS which showed breast cancer recurrence rates of 17% vs. 19% and overall survival rates of 76% and 74% for individuals that continued tamoxifen to 10 years compared with those that took it for 5 years; risk ratios for both outcomes decreased (favouring continued tamoxifen) as the trial continued.</p><p>Based on the results of ATLAS and aTTom the committee agreed that extending the duration of tamoxifen should be considered, despite the non-significant pooled effects observed for disease-free survival and overall in the evidence review.</p></div></div><div id="rl.r6"><h4>References</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref1"><p id="p-335">
|
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<strong>Davies 2013</strong>
|
|
</p>Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., Abraham, M., Medeiros Alencar, V. H., Badran, A., Bonfill, X., Bradbury, J., Clarke, M., Collins, R., Davis, S. R., Delmestri, A., Forbes, J. F., Haddad, P., Hou, M. F., Inbar, M., Khaled, H., Kielanowska, J., Kwan, W. H., Mathew, B. S., Mittra, I., Muller, B., Nicolucci, A., Peralta, O., Pernas, F., Petruzelka, L., Pienkowski, T., Radhika, R., Rajan, B., Rubach, M. T., Tort, S., Urrutia, G., Valentini, M., Wang, Y., Peto, R., Adjuvant Tamoxifen: Longer Against Shorter Collaborative Group, (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. [Erratum appears in Lancet. 2013 Mar 9;381(9869):804]. Lancet, 381, 805–16. [<a href="/pmc/articles/PMC3596060/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3596060</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23219286" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23219286</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref2"><p id="p-336">
|
|
<strong>Erman 2014</strong>
|
|
</p>Erman, A., Cost-effectiveness analysis of extended adjuvant endocrine therapy in the treatment of post-menopausal women with hormone receptor positive breast cancer. Breast Cancer Research & Treatment, 2014. 145(2): p. 267–79. [<a href="https://pubmed.ncbi.nlm.nih.gov/24771048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24771048</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref3"><p id="p-337">
|
|
<strong>Fisher 1996</strong>
|
|
</p>Fisher, B., Dignam, J., Bryant, J., DeCillis, A., Wickerham, D.L., Wolmark, N., Costantino, J., Redmond, C., Fisher, E.R., Bowman, D.M., Deschenes, L., Dimitrov, N.V., Margolese, R.G., Robidoux, A., Shibata, H., Terz, J., Paterson, A.H., Feldman, M.I., Farrar, W., Evans, J., Lickley, H.L. (1996) Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. Journal of the National Cancer Institute, 88, 1529–1542. [<a href="https://pubmed.ncbi.nlm.nih.gov/8901851" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8901851</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref4"><p id="p-338">
|
|
<strong>Fisher 2001</strong>
|
|
</p>Fisher, B., Dignam, J., Bryant, J., Wolmark, N. (2001) Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. Journal of the National Cancer Institute, 93, 684–90. [<a href="https://pubmed.ncbi.nlm.nih.gov/11333290" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11333290</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref5"><p id="p-339">
|
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<strong>Goss 2005</strong>
|
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</p>Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Cameron, D. A., Palmer, M. J., Pater, J. L. (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. Journal of the National Cancer Institute, 97, 1262–71. [<a href="https://pubmed.ncbi.nlm.nih.gov/16145047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16145047</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref6"><p id="p-340">
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<strong>Gray 2013</strong>
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</p>Gray, R. G., Rea, D., Handley, K., Bowden, S. J., Perry, P., Earl, H. M., Poole, C. J., Bates, T., Chetiyawardana, S., Dewar, J. A., Fernando, I. N., Grieve, R., Nicoll, J., Rayter, Z., Robinson, A., Salman, A., Yarnold, J., Bathers, S., Marhall, A., Lee, M. (2013). aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. Journal of Clinical Oncology, 31, 5–5.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref7"><p id="p-341">
|
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<strong>Jakesz 2007</strong>
|
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</p>Jakesz, R., Greil, R., Gnant, M., Schmid, M., Kwasny, W., Kubista, E., Mlineritsch, B., Tausch, C., Stierer, M., Hofbauer, F., Renner, K., Dadak, C., Rucklinger, E., Samonigg, H., Austrian, Breast, Colorectal Cancer Study Group (2007) Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. [Erratum appears in Journal of the National Cancer Institute 2008 Feb 6;100(3):226]. Journal of the National Cancer Institute, 99, 1845–53. [<a href="https://pubmed.ncbi.nlm.nih.gov/18073378" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18073378</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref8"><p id="p-342">
|
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<strong>Mamounas 2008</strong>
|
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</p>Mamounas, E. P., Jeong, J. H., Wickerham, D. L., Smith, R. E., Ganz, P. A., Land, S. R., Eisen, A., Fehrenbacher, L., Farrar, W. B., Atkins, J. N., Pajon, E. R., Vogel, V. G., Kroener, J. F., Hutchins, L. F., Robidoux, A., Hoehn, J. L., Ingle, J. N., Geyer, C. E., Jr., Costantino, J. P., Wolmark, N. (2008) Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. Journal of Clinical Oncology, 26, 1965–71. [<a href="https://pubmed.ncbi.nlm.nih.gov/18332472" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18332472</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref9"><p id="p-343">
|
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<strong>Muss 2008</strong>
|
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</p>Muss, H. B., Tu, D., Ingle, J. N., Martino, S., Robert, N. J., Pater, J. L., Whelan, T. J., Palmer, M. J., Piccart, M. J., Shepherd, L. E., Pritchard, K. I., He, Z., Goss, P. E. (2008) Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. Journal of Clinical Oncology, 26, 1956–64. [<a href="https://pubmed.ncbi.nlm.nih.gov/18332474" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18332474</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref10"><p id="p-344">
|
|
<strong>NICE 2009</strong>
|
|
</p>National Institute for Health and Clinical Excellence. (2009). Early and locally advanced breast cancer: diagnosis and treatment. NICE guideline (CG80). [<a href="https://pubmed.ncbi.nlm.nih.gov/19167201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19167201</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref11"><p id="p-345">
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<strong>Stewart 1996</strong>
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</p>Stewart, H. J., Forrest, A. P., Everington, D., McDonald, C. C., Dewar, J. A., Hawkins, R. A., Prescott, R. J., George, W. D. (1996) Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group. British Journal of Cancer, 74, 297–9. [<a href="/pmc/articles/PMC2074573/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2074573</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8688340" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8688340</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref12"><p id="p-346">
|
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<strong>Stewart 2001</strong>
|
|
</p>Stewart, H. J., Prescott, R. J., Forrest, A. P. (2001) Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. Journal of the National Cancer Institute, 93, 456–62. [<a href="https://pubmed.ncbi.nlm.nih.gov/11259471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11259471</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.1.ref13"><p id="p-347">
|
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<strong>Tormey 1996</strong>
|
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</p>Tormey, D.C., Gray, R., Falkson, H.C. (1996) Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. Eastern Cooperative Oncology Group. Journal of the National Cancer Institute, 88, 1828–1833. [<a href="https://pubmed.ncbi.nlm.nih.gov/8961972" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8961972</span></a>]</div></p></li></ul></div></div><div id="chd.s1.2"><h3>Review question 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in premenopausal women with oestrogen-positive breast cancer?</h3><div id="chd.s1.2.1"><h4>Introduction</h4><p>Adjuvant endocrine therapy for oestrogen positive (ER-positive) early breast cancer is well established. For premenopausal women, tamoxifen is the standard drug although the aromatase inhibitors can be given to premenopausal women if the ovaries are suppressed using gonadotropin-releasing hormone (GnRH) analogues or ablated by surgery or radiation.</p><p>Theoretically, the absence of circulating oestrogen with ovarian function suppression/ablation (OFS) in addition to tamoxifen or switching to aromatase inhibitors (which are more efficacious in postmenopausal women) should improve long term outcomes including local and distant relapse from breast cancer. However, OFS has additional side effects for young women including menopausal symptoms with the potential for additional adverse effects on bone and cardiovascular health.</p><p>International expert opinion (<a class="bibr" href="#chd.s1.2.ref4" rid="chd.s1.2.ref4">Burstein, 2016</a>) suggests premenopausal women who receive chemotherapy or are considered high risk are offered OFS while the European Society for Medical Oncology (ESMO) Clinical Practice guidelines (<a class="bibr" href="#chd.s1.2.ref8" rid="chd.s1.2.ref8">Senkus, 2015</a>) suggest a discussion with individual women based on risk and the potential side effect profile</p><p>This review aims to determine the effectiveness of OFS in addition to endocrine therapy in premenopausal women.</p></div><div id="chd.s1.2.2"><h4>PICO table</h4><p>See <a class="figpopup" href="/books/NBK576823/table/chd.tab4/?report=objectonly" target="object" rid-figpopup="figchdtab4" rid-ob="figobchdtab4">Table 4</a> for a summary of the population, intervention, comparison and outcome (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab4"><a href="/books/NBK576823/table/chd.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab4" rid-ob="figobchdtab4"><img class="small-thumb" src="/books/NBK576823/table/chd.tab4/?report=thumb" src-large="/books/NBK576823/table/chd.tab4/?report=previmg" alt="Table 4. Summary of the protocol (PICO table)." /></a><div class="icnblk_cntnt"><h4 id="chd.tab4"><a href="/books/NBK576823/table/chd.tab4/?report=objectonly" target="object" rid-ob="figobchdtab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For full details see review protocol in <a href="#chd.appa">appendix A</a>.</p></div><div id="chd.s1.2.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>; see the <a href="/books/n/niceng101erm/?report=reader" class="toc-item">methods</a> chapter for further information.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy.</p></div><div id="chd.s1.2.4"><h4>Clinical evidence</h4><div id="chd.s1.2.4.1"><h5>Included studies</h5><p>Six publications from four randomised trials (N=8762) were included in the review: Adjuvant Breast Cancer (ABC) Ovarian Ablation or Suppression Trial (k=1), E-3191 (k=1), Suppression of Ovarian Function Trial (SOFT; k=1), and Zoladex In Pre-menopausal Patients trial (ZIPP; k=3). The ABC Ovarian Ablation or Suppression Trial, E-3191 trial and the SOFT trial compare tamoxifen and ovarian suppression achieved by luteinizing-hormone releasing hormone (LHRH) agonists, oophorectomy, or radiation with tamoxifen alone, whereas the ZIPP trial compares tamoxifen and the LHRH agonist goserelin to tamoxifen alone.</p><p>All of the studies included some women with unknown, or negative oestrogen-receptor status. These studies were retained as their exclusion would have resulted in no clinical evidence for this review question. Furthermore, women in the ABC Ovarian Ablation or Suppression Trial and some women in the ZIPP trial were receiving concurrent chemotherapy. These studies were not excluded due to the small number of included studies but sensitivity analysis was planned to determine if the inclusion of such studies affects the overall estimate of effect. However, sensitivity analysis was not performed for survival outcomes as tests for heterogeneity were non-significant.</p><p>Only one study (<a class="bibr" href="#chd.s1.2.ref5" rid="chd.s1.2.ref5">Francis, 2015</a>) reported data for subgroups of interest: Age (<35/35–39/40+), grade (1/2/3), human epidermal growth factor receptor 2 (HER2) status (+/-) and previous chemotherapy (Yes/No).</p><p>The clinical studies included in this evidence review are summarised in <a class="figpopup" href="/books/NBK576823/table/chd.tab5/?report=objectonly" target="object" rid-figpopup="figchdtab5" rid-ob="figobchdtab5">Table 5</a> and evidence from these are summarised in the clinical GRADE evidence profile below (<a class="figpopup" href="/books/NBK576823/table/chd.tab6/?report=objectonly" target="object" rid-figpopup="figchdtab6" rid-ob="figobchdtab6">Table 6</a>). See also the study selection flow chart in <a href="#chd.appc">appendix C</a>, forest plots in <a href="#chd.appe">appendix E</a>, and study evidence tables in <a href="#chd.appd">appendix D</a>.</p></div><div id="chd.s1.2.4.2"><h5>Excluded studies</h5><p>Studies not included in this review with reasons for their exclusions are provided in <a href="#chd.appk">appendix K</a>.</p></div></div><div id="chd.s1.2.5"><h4>Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab5"><a href="/books/NBK576823/table/chd.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab5" rid-ob="figobchdtab5"><img class="small-thumb" src="/books/NBK576823/table/chd.tab5/?report=thumb" src-large="/books/NBK576823/table/chd.tab5/?report=previmg" alt="Table 5. Summary of included studies." /></a><div class="icnblk_cntnt"><h4 id="chd.tab5"><a href="/books/NBK576823/table/chd.tab5/?report=objectonly" target="object" rid-ob="figobchdtab5">Table 5</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. </p></div></div><p>See <a href="#chd.appd">appendix D</a> for full evidence tables.</p></div><div id="chd.s1.2.6"><h4>Quality assessment of clinical studies included in the evidence review</h4><p>The clinical evidence profile for this review question (effectiveness of ovarian suppression in addition to endocrine therapy) is presented in <a class="figpopup" href="/books/NBK576823/table/chd.tab6/?report=objectonly" target="object" rid-figpopup="figchdtab6" rid-ob="figobchdtab6">Table 6</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab6"><a href="/books/NBK576823/table/chd.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab6" rid-ob="figobchdtab6"><img class="small-thumb" src="/books/NBK576823/table/chd.tab6/?report=thumb" src-large="/books/NBK576823/table/chd.tab6/?report=previmg" alt="Table 6. Summary clinical evidence profile: Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone." /></a><div class="icnblk_cntnt"><h4 id="chd.tab6"><a href="/books/NBK576823/table/chd.tab6/?report=objectonly" target="object" rid-ob="figobchdtab6">Table 6</a></h4><p class="float-caption no_bottom_margin">Summary clinical evidence profile: Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone. </p></div></div><p>See <a href="#chd.appf">appendix F</a> for full GRADE tables.</p></div><div id="chd.s1.2.7"><h4>Economic evidence</h4><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question. Economic modelling was not undertaken for this question because other topics were agreed as higher priorities for economic evaluation.</p></div><div id="chd.s1.2.8"><h4>Evidence statements</h4><div id="chd.s1.2.8.1"><h5>Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone</h5><div id="chd.s1.2.8.1.1"><h5>Critical outcomes</h5><div id="chd.s1.2.8.1.1.1"><h5>Disease-free survival</h5><ul id="l593"><li id="lt1567" class="half_rhythm"><div>There is moderate quality evidence from 2 RCTs (N=2370) that there is no effect of ovarian suppression on disease-free survival at 5 to 9.9 year follow-up in mixed populations of pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1568" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=233) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer aged <35 years.</div></li><li id="lt1569" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=387) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer aged 35 to 39 years.</div></li><li id="lt1570" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1413) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer aged >40 years.</div></li><li id="lt1571" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=540) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with grade 1, ER positive invasive breast cancer.</div></li><li id="lt1572" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1006) that ovarian suppression plus tamoxifen produces a clinically meaningful improvement in disease-free at 5 year follow-up compared with tamoxifen alone for pre-menopausal women with grade 2, ER positive invasive breast cancer.</div></li><li id="lt1573" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=439) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with grade 3, ER positive invasive breast cancer.</div></li><li id="lt1574" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1724) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with HER2 negative, ER positive invasive breast cancer.</div></li><li id="lt1575" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=236) that ovarian suppression plus tamoxifen produces a clinically meaningful improvement in disease-free at 5 year follow-up compared with tamoxifen alone for pre-menopausal women with HER2 positive, ER positive invasive breast cancer.</div></li><li id="lt1576" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1084) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer who have had chemotherapy.</div></li><li id="lt1577" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=949) that there is no effect of ovarian suppression on disease-free survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer who have not had chemotherapy.</div></li></ul></div><div id="chd.s1.2.8.1.1.2"><h5>Treatment-related morbidity</h5><ul id="l594"><li id="lt1578" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=920) that ovarian suppression plus tamoxifen produces clinically meaningful increases in vasodilation compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1579" class="half_rhythm"><div>There is very low quality evidence from 2 RCTs (N=1265) that ovarian suppression plus tamoxifen produces clinically meaningful increases in weight gain compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1580" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=920) that ovarian suppression plus tamoxifen produces clinically meaningful increases in arthralgia compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1581" class="half_rhythm"><div>There is low quality evidence from 3 RCTs (N=3276) that ovarian suppression plus tamoxifen produces clinically meaningful increases in anxiety/depression/irritability compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1582" class="half_rhythm"><div>There is low quality evidence from 2 RCTs (N=1265) that ovarian suppression plus tamoxifen produces clinically meaningful increases in sweating compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1583" class="half_rhythm"><div>There is low quality evidence from 2 RCTs (N=2356) that ovarian suppression plus tamoxifen produces clinically meaningful increases in grade 3+ hot flushes at 3 to 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1584" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that ovarian suppression plus tamoxifen produces clinically meaningful increases in grade 3+ hypertension at 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1585" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that ovarian suppression plus tamoxifen produces clinically meaningful reductions in grade 3+ cardiac ischemia or infarction at 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1586" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that there is no effect of ovarian suppression on grade 3+ thrombosis or embolism at 5.6 year follow-up for premenopausal women with ER positive invasive breast cancer.</div></li><li id="lt1587" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that there is no effect of ovarian suppression on grade 3+ musculoskeletal symptoms at 5.6 year follow-up for premenopausal women with ER positive invasive breast cancer.</div></li><li id="lt1588" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that ovarian suppression plus tamoxifen produces clinically meaningful increases in grade 3+ osteoporosis at 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1589" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that there is no effect of ovarian suppression on grade 3+ fractures at 5.6 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1590" class="half_rhythm"><div>There is moderate quality evidence from 2 RCTs (N=2356) that there is no effect of ovarian suppression on vaginal dryness at 3 to 5.6 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1591" class="half_rhythm"><div>There is moderate quality evidence from 2 RCTs (N=2356) that there is no effect of ovarian suppression on changes in libido at 3 to 5.6 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1592" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that ovarian suppression plus tamoxifen produces clinically meaningful reductions in grade 3+ CNS cerebrovascular ischemia at 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1593" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=2011) that ovarian suppression plus tamoxifen produces clinically meaningful increases in grade 3+ CNS haemorrhage at 5.6 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer. However, the effect was not statistically significant.</div></li><li id="lt1594" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=60) that there is no effect of ovarian suppression on vasomotor symptoms measured by Physical Symptoms and Problem List at 3 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1595" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=63) that there is no effect of ovarian suppression on vaginal dryness measured by Physical Symptoms and Problem List at 3 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1596" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=32) that there is no effect of ovarian suppression on bone density at 2 year follow-up for pre-menopausal women with ER positive invasive breast cancer.</div></li></ul></div><div id="chd.s1.2.8.1.1.3"><h5>Health-related quality of life</h5><ul id="l595"><li id="lt1597" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=188) that there is no effect of ovarian suppression on HRQoL measured by the FACT-G for pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1598" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=177) that there is no effect of ovarian suppression on HRQoL measured by the FACT-B for pre-menopausal women with ER positive invasive breast cancer.</div></li></ul></div></div><div id="chd.s1.2.8.1.2"><h5>Important outcomes</h5><div id="chd.s1.2.8.1.2.1"><h5>Local recurrence rate</h5><ul id="l596"><li id="lt1599" class="half_rhythm"><div>No evidence was found for this outcome.</div></li></ul></div><div id="chd.s1.2.8.1.2.2"><h5>Overall survival</h5><ul id="l597"><li id="lt1600" class="half_rhythm"><div>There is low quality evidence from 4 RCTs (N=4108) that ovarian suppression plus tamoxifen produces a clinically meaningful improvement in overall survival at 5 to 9.9 year follow-up compared with tamoxifen alone for mixed populations of pre-menopausal women with ER positive invasive breast cancer.</div></li><li id="lt1601" class="half_rhythm"><div>There is low quality evidence from one RCT (N=1084) that ovarian suppression plus tamoxifen produces a clinically meaningful improvement in overall survival at 5 year follow-up compared with tamoxifen alone for pre-menopausal women with ER positive invasive breast cancer who had received chemotherapy.</div></li><li id="lt1602" class="half_rhythm"><div>There is low quality evidence from one RCT (N=949) that there is no effect of ovarian suppression on overall survival at 5 year follow-up for pre-menopausal women with ER positive invasive breast cancer who had not received chemotherapy.</div></li></ul></div><div id="chd.s1.2.8.1.2.3"><h5>Compliance</h5><ul id="l598"><li id="lt1603" class="half_rhythm"><div>There is moderate quality evidence from one RCT (N=227) that there is no effect of ovarian suppression on rates of treatment completion in pre-menopausal women with ER positive invasive breast cancer who had received chemotherapy.</div></li></ul></div><div id="chd.s1.2.8.1.2.4"><h5>Treatment-related mortality</h5><ul id="l599"><li id="lt1604" class="half_rhythm"><div>No evidence was found for this outcome.</div></li></ul></div></div></div></div><div id="chd.s1.2.9"><h4>The committee’s discussion of the evidence</h4><div id="chd.s1.2.9.1"><h5>Interpreting the evidence</h5><div id="chd.s1.2.9.1.1"><h5>The outcomes that matter most</h5><p>The committee prioritised disease-free survival, treatment-related morbidity and health-related quality of life as critical outcomes; the latter outcomes were prioritised over overall survival due to the significant side-effect profile associated with ovarian suppression, including menopausal symptoms and the fact that conception is not possible or not advised for the duration of treatment. This meant that the disease-free survival benefits would need to be balanced against the side-effects. Overall survival, local recurrence rate, compliance with treatment, and treatment-related mortality were selected as important outcomes.</p><p>There was no evidence available for local recurrence rate or treatment-related mortality.</p></div><div id="chd.s1.2.9.1.2"><h5>The quality of the evidence</h5><p>The quality of the evidence for this review was assessed using GRADE. For disease-free survival the evidence was moderate quality for the sample as a whole, but low quality for all the subgroups due to small number of events of interest. The evidence was down-graded because of a risk of bias due to unclear randomisation and allocation concealment procedures.</p><p>For treatment-related morbidity the evidence quality ranged from very low to moderate, and was downgraded mainly due to uncertainty in the estimate due to the low number of events of interest, but also because of issues with risk of bias due to unclear randomisation and allocation concealment procedures, and indirectness due to concurrent chemotherapy administration in the ZIPP and ABC trials.</p><p>Health-related quality of life evidence was moderate for FACT-B and very low for FACT-G. This was because of risk of bias due to unclear randomisation and allocation concealment procedures for both scales. In addition, the evidence for FACT-G was downgraded because of imprecision due to a wide confidence interval and therefore uncertainty about the estimate.</p><p>Overall survival evidence was of low quality, and compliance evidence was also moderate due to a small number of events of interest.</p><p>Due to the quality of the evidence and the lack of benefit reported for the critical outcome of disease-free survival, the committee could only make a weak recommendation for the use of OFS. However, the evidence for the important outcome of overall survival was of moderate quality and showed benefit in the mixed population and those who had received chemotherapy so the committee also made a recommendation that this information should be taken into account.</p></div><div id="chd.s1.2.9.1.3"><h5>Benefits and harms</h5><p>The benefits of OFS in addition to endocrine therapy include improvements in disease-free and overall survival. There is a 1% improvement in overall survival at 5 years in the mixed population, and a 3% improvement in those who had received chemotherapy. There was also a 2% increase in disease-free survival but these results were not significant</p><p>It is accepted that OFS will lead to symptoms of early menopause. Whilst symptoms related to this were not all significantly increased in the current evidence review (based on very low to low quality evidence), there were increases in weight gain (number need to harm, NNH, 33), hot flushes (NNH=14), vasodilation (NNH=4) and sweating (NNH=33). In addition, women will be infertile for the duration of treatment, although women would normally be advised not to become pregnant while taking tamoxifen so the OFS may have limited additional impact in this respect.</p><p>The committee discussed the balance of benefits and harms, noting that menopausal symptoms and fertility will return after OFS treatment is ended (provided natural menopause has not been reached during this time), and that low to moderate quality evidence found that OFS had no effect on quality of life. In addition, the committee agreed that people tend to prioritise survival over side-effects, and that discussing the potential benefits/harms with women, and targeting those who are most likely to gain benefit (i.e. those who have had a risk deemed high enough to be offered chemotherapy) should help balance the acceptability of treatment side-effects in relation to the perceived risk to the patient.</p></div></div><div id="chd.s1.2.9.2"><h5>Cost effectiveness and resource use</h5><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question.</p><p>The committee discussed the potential costs and savings of recommendations and thought that there could be additional costs associated with the use of ovarian suppression. As well as the costs of the ovarian suppression medication, there would also be costs associated with administration (monthly injections at GP surgery given by a practice nurse). There could also be additional appointments (and potentially procedures) required for the management of menopausal symptoms. For example, bone health monitoring using dual-energy X-ray absorptiometry may be required.</p><p>The committee thought that any additional costs associated with ovarian suppression would be offset, at least partially, by savings resulting from improvements in disease related outcomes (DFS and OS). These improvements should reduce the need (or at least delay the need) for future procedures, treatments and hospice care.</p><p>Overall, the committee did not anticipate that their recommendations would have a substantial resource impact. The committee noted that ovarian function suppression is already given in many centres and so the nationwide cost of implementing the recommendations is not anticipated to exceed £1 million per year. However there would be increased costs in those centres not currently offering ovarian function suppression.</p></div><div id="chd.s1.2.9.3"><h5>Other factors the committee took into account</h5><p>The committee gave greater weight to the SOFT and ECOG trial data from this evidence review as they identified three potential problems with the ABC and ZIPP studies that they believed reduced the applicability of this data to current practice. Firstly, in the ABC study women were given ovarian function suppression for 2 years and in the ZIPP study for 2–3 years. However, current standard practice is to give endocrine therapy (and therefore OFS) for at least 5 years. Secondly, the ZIPP and ABC studies both included chemotherapy administered concurrently with OFS and tamoxifen, and <a class="bibr" href="#chd.s1.2.ref2" rid="chd.s1.2.ref2">Albain (2009)</a> showed that this combination is inferior. Thirdly, the SOFT trial confirmed that ovarian function had returned after chemotherapy whereas other trials did not confirm this; therefore it is possible that ovaries were not functioning in control arm.</p><p>In addition to the evidence presented in the evidence review the committee were aware of a combined analysis from two studies, SOFT and Tamoxifen and Exemestane Trial (TEXT; <a class="bibr" href="#chd.s1.2.ref7" rid="chd.s1.2.ref7">Pagani, 2014</a>). This combined analysis showed greater benefit for OFS and AI whereas our current studies all used tamoxifen. Therefore, the committee have recommended considering OFS in addition to endocrine therapy despite the lack of significant disease-free survival benefit as a greater effect may have been observed if AIs had been used; a specific drug has not been recommended for endocrine therapy to allow clinician discretion to use AIs or tamoxifen as considered appropriate.</p></div></div><div id="rl.r7"><h4>References</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref1"><p id="p-672">
|
|
<strong>Adjuvant Breast Cancer Trials Collaborative Group 2007</strong>
|
|
</p>Adjuvant Breast Cancer Trials Collaborative Group (2007) Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. Journal of the National Cancer Institute, 99, 516–25. [<a href="https://pubmed.ncbi.nlm.nih.gov/17405996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17405996</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref2"><p id="p-673">
|
|
<strong>Albain 2009</strong>
|
|
</p>Albain, K. S., Barlow, W. E., Ravdin, P. M., Farrar, W. B., Burton, G. V., Ketchel, S. J., Cobau, C. D., Levine, E. G., Ingle, J. N., Pritchard, K. I., Lichter, A. S., Scheider, D. J., Abeloff, M. D., Henderson, I. C., Muss, H. B., Green, S. J., Lew, D., Livingston, R. B., Martino, S., Osborne, C. K. (2009). Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. The Lancet, 374, 2055–2063. [<a href="/pmc/articles/PMC3140679/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3140679</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20004966" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20004966</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref3"><p id="p-674">
|
|
<strong>Baum 2006</strong>
|
|
</p>Baum, M., Hackshaw, A., Houghton, J., Rutqvist,, Fornander, T., Nordenskjold, B., Nicolucci, A., Sainsbury, R., Zipp International Collaborators Group (2006) Adjuvant goserelin in premenopausal patients with early breast cancer: Results from the ZIPP study. European journal of cancer, 42, 895–904. [<a href="https://pubmed.ncbi.nlm.nih.gov/16545560" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16545560</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref4"><p id="p-675">
|
|
<strong>Burstein 2016</strong>
|
|
</p>Burstein, H. J., Lacchetti, C., Anderson
|
|
H., Buccholz, T. A., Davidson, N. E., Gelmon, K. E., Giordano, S. H., Hudis, C. A., Solky, A. J., Steams, V., Wimer, E. P., Griggs, J. J. (2016). Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. Journal of Clinical Oncology, 10, 1689–1701. [<a href="https://pubmed.ncbi.nlm.nih.gov/26884586" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26884586</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref5"><p id="p-676">
|
|
<strong>Francis 2015</strong>
|
|
</p>Francis, P. A., Regan, M. M., Fleming, G. F., Lang, I., Ciruelos, E., Bellet, M., Bonnefoi, H. R., Climent, M. A., Da Prada, G. A., Burstein, H. J., Martino, S., Davidson, N. E., Geyer, C. E., Jr., Walley, B. A., Coleman, R., Kerbrat, P., Buchholz, S., Ingle, J. N., Winer, E. P., Rabaglio-Poretti, M., Maibach, R., Ruepp, B., Giobbie-Hurder, A., Price, K. N., Colleoni, M., Viale, G., Coates, A. S., Goldhirsch, A., Gelber, R. D., Soft Investigators, International Breast Cancer Study, Group (2015) Adjuvant ovarian suppression in premenopausal breast cancer. New England Journal of Medicine, 372, 436–46. [<a href="/pmc/articles/PMC4341825/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4341825</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25495490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25495490</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref6"><p id="p-677">
|
|
<strong>Nystedt 2003</strong>
|
|
</p>Nystedt, M., Berglund, G., Bolund, C., Fornander, T., Rutqvist, L.E., (2003) Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study. Journal of Clinical Oncology, 21, 1836–1844. [<a href="https://pubmed.ncbi.nlm.nih.gov/12721261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12721261</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref7"><p id="p-678">
|
|
<strong>Pagani 2014</strong>
|
|
</p>Pagani, O., Regan, M. M., Walley, B. A., Fleming, G. F., Colleoni, M., Láng, I., Gomez, H. L., Tondini, C., Burstein, H. J., Perez, E. A., Ciruelos, E., Stearns, V., Bonnefoi, H. R., Martino, S., Geyer
|
|
Jr., C. E., Pinotti, G., Puglisi, F., Crivellari, D., Ruhstaller, R., Winer, E. P., Rabaglio-Poretti, M., Maibach, R., Ruepp, B., Giobbie-Hurder, A., Price, K. N., Bernhard, J., Luo, W., Ribi, K., Viale
|
|
G., Coates, A. S., Gelber, R. D., Goldhirsch, A., Francis, P. A., TEXT and SOFT Investigators and the International Breast Cancer Study Group. (2014). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. The New England Journal of Medicine, 371, 107–118. [<a href="/pmc/articles/PMC4175521/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4175521</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24881463" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24881463</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref8"><p id="p-679">
|
|
<strong>Senkus 2015</strong>
|
|
</p>Senkus, E., Kyriakides, S., Ohno, S., Penualt-Llorca, F., Poortmans, P., Rutgers, E., Zacrisson, S., Cardoso, F., ESMO Guidelines Committee (2015). Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 25, v8–v30. [<a href="https://pubmed.ncbi.nlm.nih.gov/26314782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26314782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref9"><p id="p-680">
|
|
<strong>Sverrisdottir 2004</strong>
|
|
</p>Sverrisdottir, A., Fornander, T., Jacobsson, H., von Schoultz, E., Rutqvist, L. E., (2004) Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy. Journal of Clinical Oncology, 22, 3694–9. [<a href="https://pubmed.ncbi.nlm.nih.gov/15365065" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15365065</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.2.ref10"><p id="p-681">
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<strong>Tevaarwerk 2014</strong>
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</p>Tevaarwerk, A. J., Wang, M., Zhao, F., Fetting, J. H., Cella, D., Wagner, L. I., Martino, S., Ingle, J. N., Sparano, J. A., Solin, L. J., Wood, W. C., Robert, N. J., (2014) Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): A trial of the eastern cooperative oncology group. Journal of Clinical Oncology, 32, 3948–3958. [<a href="/pmc/articles/PMC4251958/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4251958</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25349302" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25349302</span></a>]</div></p></li></ul></div></div><div id="chd.s1.3"><h3>Review question 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h3><div id="chd.s1.3.1"><h4>Introduction</h4><p>Ductal carcinoma in situ (DCIS) is non-invasive and considered the earliest form of breast cancer. Abnormal cells are located inside milk ducts in the breast and have not spread or invaded other parts of the breast. Its detection has significantly increased since routine mammographic screening. The management of DCIS includes surgical intervention and with radiotherapy as appropriate.</p><p>Chemoprevention may be used in people who have been treated for DCIS to prevent the development of breast cancer. The most commonly used chemoprevention is with hormone therapy involving oestrogen receptor (ER) blockers (tamoxifen or raloxifene) or aromatase inhibitors (AIs; anastrozole, exemestane and letrozole). These hormone therapies are an established treatment for women with ER-positive invasive breast cancer. At the time of the previous guideline CG80 (<a class="bibr" href="#chd.s1.3.ref5" rid="chd.s1.3.ref5">NICE 2009</a>), evidence was felt to be conflicting around use of hormonal therapies (chemoprevention) after adequate surgical treatment of DCIS.</p><p>The aim of this review is to assess the role of chemoprevention in women with DCIS, which will consider the benefits of reducing breast cancer recurrence and secondary breast cancers, compared to the side effects of increased risks of endometrial cancers and thromboembolic complications.</p></div><div id="chd.s1.3.2"><h4>PICO table</h4><p>See <a class="figpopup" href="/books/NBK576823/table/chd.tab7/?report=objectonly" target="object" rid-figpopup="figchdtab7" rid-ob="figobchdtab7">Table 7</a> for a summary of the population, intervention, comparison and outcome (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab7"><a href="/books/NBK576823/table/chd.tab7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab7" rid-ob="figobchdtab7"><img class="small-thumb" src="/books/NBK576823/table/chd.tab7/?report=thumb" src-large="/books/NBK576823/table/chd.tab7/?report=previmg" alt="Table 7. Summary of the protocol (PICO table)." /></a><div class="icnblk_cntnt"><h4 id="chd.tab7"><a href="/books/NBK576823/table/chd.tab7/?report=objectonly" target="object" rid-ob="figobchdtab7">Table 7</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For full details see review protocol in <a href="#chd.appa">appendix A</a>.</p></div><div id="chd.s1.3.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>; see the <a href="/books/n/niceng101erm/?report=reader" class="toc-item">methods</a> chapter for further information.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy.</p></div><div id="chd.s1.3.4"><h4>Clinical evidence</h4><div id="chd.s1.3.4.1"><h5>Included studies</h5><p>Four studies (n=3,496) identified by the literature search were included in the review (<a class="bibr" href="#chd.s1.3.ref1" rid="chd.s1.3.ref1">Cuzick, 2011</a>; <a class="bibr" href="#chd.s1.3.ref3" rid="chd.s1.3.ref3">Fisher, 1999</a>, <a class="bibr" href="#chd.s1.3.ref4" rid="chd.s1.3.ref4">Guerrieri-Gonzaga, 2006</a>; <a class="bibr" href="#chd.s1.3.ref6" rid="chd.s1.3.ref6">Wapnir, 2011</a>), which report data from 3 trials: <a class="bibr" href="#chd.s1.3.ref4" rid="chd.s1.3.ref4">Guerrieri-Gonzaga, 2006</a> (k=1), National Surgical Adjuvant Breast and Bowel Project (NSAPB) B34 (k=2), and UK, Australia and New Zealand (UK/ANZ; k=1).</p><p>All included studies compared tamoxifen against no chemoprevention. Three studies reported data for critical outcomes for subgroups of interest: breast-conserving surgery (BCS) followed by radiotherapy (k=3) and BCS with no radiotherapy (k=1). No evidence was available for chemoprevention following mastectomy.</p><p>The clinical studies included in this evidence review are summarised in <a class="figpopup" href="/books/NBK576823/table/chd.tab8/?report=objectonly" target="object" rid-figpopup="figchdtab8" rid-ob="figobchdtab8">Table 8</a> and evidence from these are summarised in the clinical GRADE evidence profile below (<a class="figpopup" href="/books/NBK576823/table/chd.tab9/?report=objectonly" target="object" rid-figpopup="figchdtab9" rid-ob="figobchdtab9">Table 9</a>). See also the study selection flow chart in <a href="#chd.appc">appendix C</a>, forest plots in <a href="#chd.appe">appendix E</a>, and study evidence tables in <a href="#chd.appd">appendix D</a>.</p></div><div id="chd.s1.3.4.2"><h5>Excluded studies</h5><p>Studies not included in this review with reasons for their exclusions are provided in <a href="#chd.appk">appendix K</a>.</p></div></div><div id="chd.s1.3.5"><h4>Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab8"><a href="/books/NBK576823/table/chd.tab8/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab8" rid-ob="figobchdtab8"><img class="small-thumb" src="/books/NBK576823/table/chd.tab8/?report=thumb" src-large="/books/NBK576823/table/chd.tab8/?report=previmg" alt="Table 8. Summary of included studies." /></a><div class="icnblk_cntnt"><h4 id="chd.tab8"><a href="/books/NBK576823/table/chd.tab8/?report=objectonly" target="object" rid-ob="figobchdtab8">Table 8</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. </p></div></div><p>See <a href="#chd.appd">appendix D</a> for full evidence tables.</p></div><div id="chd.s1.3.6"><h4>Quality assessment of clinical studies included in the evidence review</h4><p>The clinical evidence profile for this review question (chemoprevention in DCIS) is presented in <a class="figpopup" href="/books/NBK576823/table/chd.tab9/?report=objectonly" target="object" rid-figpopup="figchdtab9" rid-ob="figobchdtab9">Table 9</a>. The quality of evidence ranges from very low to high. Main reasons for downgrading evidence was imprecision around the estimates due to a small number of events of interest and wide confidence intervals.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdtab9"><a href="/books/NBK576823/table/chd.tab9/?report=objectonly" target="object" title="Table 9" class="img_link icnblk_img figpopup" rid-figpopup="figchdtab9" rid-ob="figobchdtab9"><img class="small-thumb" src="/books/NBK576823/table/chd.tab9/?report=thumb" src-large="/books/NBK576823/table/chd.tab9/?report=previmg" alt="Table 9. Summary clinical evidence profile: Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS." /></a><div class="icnblk_cntnt"><h4 id="chd.tab9"><a href="/books/NBK576823/table/chd.tab9/?report=objectonly" target="object" rid-ob="figobchdtab9">Table 9</a></h4><p class="float-caption no_bottom_margin">Summary clinical evidence profile: Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS. </p></div></div><p>See <a href="#chd.appf">appendix F</a> for full GRADE tables.</p></div><div id="chd.s1.3.7"><h4>Economic evidence</h4><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question. Economic modelling was not undertaken for this question because other topics were agreed as higher priorities for economic evaluation.</p></div><div id="chd.s1.3.8"><h4>Evidence statements</h4><div id="chd.s1.3.8.1"><h5>Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS</h5><div id="chd.s1.3.8.1.1"><h5>Critical outcomes</h5><div id="chd.s1.3.8.1.1.1"><h5>Disease-free survival</h5><ul id="l611"><li id="lt1630" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=1576) that tamoxifen produces clinically meaningful increases in disease-free survival compared with no chemoprevention at 10 year follow-up for people with excised DCIS.</div></li><li id="lt1631" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=523) that there is no clinically important effect of tamoxifen on disease-free survival at 10 year follow-up for people with excised DCIS following BCS and radiotherapy.</div></li><li id="lt1632" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1053) that tamoxifen produces clinically meaningful increases in disease-free survival compared with no chemoprevention at 10 year follow-up for people with excised DCIS following BCS alone.</div></li></ul></div><div id="chd.s1.3.8.1.1.2"><h5>Local recurrence</h5><ul id="l612"><li id="lt1633" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1576) that tamoxifen produces clinically meaningful reductions in local recurrence compared with no chemoprevention at 10 year follow-up for people with excised DCIS.</div></li><li id="lt1634" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1799) that tamoxifen produces clinically meaningful reductions in invasive local recurrence compared with no chemoprevention at 13.6 year follow-up for people with excised DCIS following BCS and radiotherapy.</div></li><li id="lt1635" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1799) that there is no clinically important effect of tamoxifen on DCIS local recurrence at 13.6 year follow-up for people with excised DCIS following BCS and radiotherapy.</div></li><li id="lt1636" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=523) that there is no clinically important effect of tamoxifen on local recurrence at 10 year follow-up for people with excised DCIS following BCS and radiotherapy.</div></li><li id="lt1637" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1053) that tamoxifen produces clinically meaningful reductions in local recurrence compared with no chemoprevention at 10 year follow-up for people with excised DCIS following BCS alone.</div></li></ul></div><div id="chd.s1.3.8.1.1.3"><h5>Treatment-related morbidity</h5><ul id="l613"><li id="lt1638" class="half_rhythm"><div>There is high quality evidence from 2 RCTs (N=1897) that tamoxifen produces clinically meaningful increases in vaginal dryness/discharge at 3.3 to 6.2 year follow-up compared with no chemoprevention for people with excised DCIS.</div></li><li id="lt1639" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1781) that tamoxifen produces clinically meaningful increases in grade 3+ toxicities at 6.2 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1640" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1781) that tamoxifen produces clinically meaningful increases in phlebitis/thromboembolisms at 6.2 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1641" class="half_rhythm"><div>There is low quality evidence from 1 RCT (N=1781) that there is no clinically important effect of tamoxifen on mood changes at 6.2 year follow-up for people with excised DCIS.</div></li><li id="lt1642" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1781) that there is no clinically important effect of tamoxifen on menstrual disorders at 6.2 year follow-up for people with excised DCIS.</div></li><li id="lt1643" class="half_rhythm"><div>There is high quality evidence from 2 RCTs (N=1897) that there is no clinically important effect of tamoxifen on hot flashes at 3.3 to 6.2 year follow-up for people with excised DCIS.</div></li><li id="lt1644" class="half_rhythm"><div>There is high quality evidence from 1 RCT (N=1781) that there is no clinically important effect of tamoxifen on fluid retention at 6.2 year follow-up for people with excised DCIS.</div></li><li id="lt1645" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that tamoxifen produces clinically meaningful reductions in ocular/visual treatment-related morbidities at 3.3 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1646" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that tamoxifen produces clinically meaningful reductions in dermatological treatment-related morbidities at 3.3 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1647" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that there is no clinically important effect of tamoxifen on dysuria/incontinence at 3.3 year follow-up for people with excised DCIS.</div></li><li id="lt1648" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that tamoxifen produces clinically meaningful increases in vaginal bleeding at 3.3 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1649" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that tamoxifen produces clinically meaningful increases in endometrial polyps at 3.3 year follow-up compared with no chemoprevention for people with excised DCIS. However, the effect was not statistically significant.</div></li><li id="lt1650" class="half_rhythm"><div>There is very low quality evidence from 1 RCT (N=116) that there is no clinically important effect of tamoxifen on sweats/weight gain at 3.3 year follow-up for people with excised DCIS.</div></li></ul></div></div><div id="chd.s1.3.8.1.2"><h5>Important outcomes</h5><div id="chd.s1.3.8.1.2.1"><h5>Health-related quality of life</h5><ul id="l614"><li id="lt1651" class="half_rhythm"><div>No evidence was found for this outcome.</div></li></ul></div><div id="chd.s1.3.8.1.2.2"><h5>Overall survival</h5><ul id="l615"><li id="lt1652" class="half_rhythm"><div>There is moderate quality evidence from 1 RCT (N=1799) that there is no clinically important effect of tamoxifen on overall survival at 13.6 year follow-up for people with excised DCIS following BCS and radiotherapy.</div></li></ul></div><div id="chd.s1.3.8.1.2.3"><h5>Treatment adherence</h5><ul id="l616"><li id="lt1653" class="half_rhythm"><div>No evidence was found for this outcome.</div></li></ul></div></div></div></div><div id="chd.s1.3.9"><h4>Economic evidence</h4><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question. Economic modelling was not undertaken for this question because other topics were agreed as higher priorities for economic evaluation.</p></div><div id="chd.s1.3.10"><h4>The committee’s discussion of the evidence</h4><div id="chd.s1.3.10.1"><h5>Interpreting the evidence</h5><div id="chd.s1.3.10.1.1"><h5>The outcomes that matter most</h5><p>Disease-free survival, local recurrence and treatment related-morbidity were selected by the committee as the critical outcomes for this review. Local recurrence was prioritised over overall survival as this review question is examining whether chemoprevention is effective at preventing invasive cancer and return of DCIS in people following treatment of DCIS. DCIS itself does not usually have an impact on overall survival, except by increasing the chance of invasive cancer developing. Treatment-related morbidity also critical as it affects the tolerance of, and adherence to treatment, and quality of life.</p><p>Overall survival, HRQoL and treatment adherence were defined as the important outcomes, but no evidence for HRQoL or treatment adherence was identified.</p></div><div id="chd.s1.3.10.1.2"><h5>The quality of the evidence</h5><p>The quality of the evidence was assessed using GRADE. For disease-free survival the evidence was of a high-moderate quality, with the downgrading to moderate mainly due to a small number of events of interest.</p><p>For local recurrence and overall survival the evidence was of moderate quality, again downgraded due to small number of events of interest.</p><p>The quality of evidence for treatment-related morbidities ranged from high to very low. The main reason for downgrading here was a small number of events and a wide confidence interval.</p><p>The recommendations are based on the strong evidence of the benefits of chemoprevention in terms of disease-free survival and local recurrence for those people who do not have radiotherapy.</p></div><div id="chd.s1.3.10.1.3"><h5>Benefits and harms</h5><p>The evidence review identified specific benefits of chemoprevention for people with DCIS who do not have radiotherapy: there was an 8% improvements in DFS at 10 years (NNT 13) and 5% improvement in local recurrence at 10 years (NNT 10).</p><p>The main harm identified in the evidence review was a 12% increase in vaginal dryness in those women treated with tamoxifen compared with no chemoprevention (NNH 8). There was also an increased rate of endometrial polyps and thrombophlebitis in the tamoxifen arm but this was not statistically significant.</p><p>However, the committee knew from their clinical experience that the occurrence of menopausal symptoms with endocrine therapy is well established (despite lack of evidence in current review) and that this may lead to reduced adherence.</p><p>Pre-menopausal women who wish to have children may be less willing to take tamoxifen as, due to its potential teratogenic effects, conception is not recommended for the duration of the tamoxifen treatment.</p><p>The committee balanced the benefits and harms of chemoprevention in this population, and took into consideration the fact that the benefits relate to DFS and local recurrence rather than overall survival. There was no evidence available to stratify high and low risk populations in the current review; however, the committee felt there was a risk of over-treatment if chemoprevention was offered to everyone, and the potential amount of benefit would be proportional to the individual’s risk level. The committee therefore chose to stratify the population for risk by assessing if they would have been offered radiotherapy.</p><p>Based on this stratification, the committee recommended chemoprevention is offered to those who are recommended radiotherapy but do not have it, and is considered for those who are not recommended radiotherapy, but that the benefits and risks are discussed with the woman.</p></div></div><div id="chd.s1.3.10.2"><h5>Cost effectiveness and resource use</h5><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question.</p><p>The recommendation to offer endocrine therapy may require an increase in resources. However, the cost impact is likely to be minimal as DCIS affects a relatively small number of people in the UK and chemoprevention drugs are inexpensive. In addition to drug costs, there may be some additional monitoring by GP required for people receiving chemoprevention but this would probably be limited to an annual check-up except in people experiencing side effects. The upfront costs associated with the use of chemoprevention are likely to be offset, at least partially, by downstream savings associated with preventing recurrences and future treatment.</p></div><div id="chd.s1.3.10.3"><h5>Other factors the committee took into account</h5><p>The only drug looked at in this evidence review was tamoxifen as trials of others were not available. However other drugs are available for endocrine chemoprevention and the committee agreed that benefits of other endocrine therapies were likely to be very similar in this population. The committee therefore recommended endocrine chemoprevention, rather than specifically tamoxifen.</p><p>The committee did not make a research recommendation to address the lack of data for other drugs in this situation as they were aware of other trials (e.g., International Breast Cancer Intervention Studies [IBIS]-II; <a class="bibr" href="#chd.s1.3.ref2" rid="chd.s1.3.ref2">Cuzick, 2014</a>) comparing aromatase inhibitors with tamoxifen; this trial did not meet our inclusion criteria as it compared two different forms of endocrine chemoprevention rather than comparing endocrine chemoprevention with no chemoprevention.</p><p>The recommendations made are specific to ER-positive women. This was not specified in the protocol but it is well established that only those with ER-positive DCIS will benefit from endocrine therapy and therefore it would be inappropriate to offer endocrine chemoprevention to ER-negative women.</p></div></div><div id="rl.r8"><h4>References</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref1"><p id="p-895">
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<strong>Cuzick 2011</strong>
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</p>Cuzick, J., Sestak, I., Pinder, S. E., Ellis, I. O., Forsyth, S., Bundred, N. J., Forbes, J. F., Bishop, H., Fentiman, I. S., George, W. D. (2011) Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: Long-term results from the UK/ANZ DCIS trial. Lancet Oncology, 12, 21–29. [<a href="/pmc/articles/PMC3018565/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3018565</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21145284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21145284</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref2"><p id="p-896">
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<strong>Cuzick 2014</strong>
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</p>Cuzick, J., Sestak, I., Forbes, J. F., Dowsett, M., Knox, J., Cawthorn, S., Saunders, C., Roche, N., Mansel, R. E., von Minckwitz, G., Bonanni, B., Palva, T., Howell, A., IBIS-II investigators. (2014). Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. The Lancet, 383, 1041–1048. [<a href="https://pubmed.ncbi.nlm.nih.gov/24333009" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24333009</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref3"><p id="p-897">
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<strong>Fisher 1999</strong>
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</p>Fisher, B., Dignam, J., Wolmark, N., Wickerham, D. L., Fisher, E. R., Mamounas, E., Smith, R., Begovic, M., Dimitrov, N. V., Margolese, R. G., Kardinal, C. G., Kavanah, M. T., Fehrenbacher, L., Oishi, R. H. (1999) Tamoxifen in treatment of intraductal breast cancer: National surgical adjuvant breast and bowel project B-24 randomised controlled trial. Lancet, 353, 1993–2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10376613" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10376613</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref4"><p id="p-898">
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<strong>Guerrieri-Gonzaga 2006</strong>
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</p>Guerrieri-Gonzaga, A., Robertson, C., Bonanni, B., Serrano, D., Cazzaniga, M., Mora, S., Gulisano, M., Johansson, H., Intra, M., Latronico, A., Franchi, D., Pelosi, G., Johnson, K., Decensi, A. (2006) Preliminary results on safety and activity of a randomized, double-blind, 2 X 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in premenopausal women. [Erratum: 2006; 24(19): 3321]. Journal of Clinical Oncology, 24, 129–135. [<a href="https://pubmed.ncbi.nlm.nih.gov/16382122" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16382122</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref5"><p id="p-899">
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<strong>NICE 2009</strong>
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</p>National Institute for Health and Clinical Excellence. (2009) Early and locally advanced breast cancer: diagnosis and treatment. NICE guideline (CG80). [<a href="https://pubmed.ncbi.nlm.nih.gov/19167201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19167201</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd.s1.3.ref6"><p id="p-900">
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<strong>Wapnir 2011</strong>
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</p>Wapnir, I. L., Dignam, J. J., Fisher, B., Mamounas, E. P., Anderson, S. J., Julian, T. B., Land, S. R., Margolese, R. G., Swain, S. M., Costantino, J. P., Wolmark, N. (2011) Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. Journal of the National Cancer Institute, 103, 478–88. [<a href="/pmc/articles/PMC3107729/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3107729</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21398619" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21398619</span></a>]</div></p></li></ul></div></div></div><div id="appendixes.appgroupd"><h2 id="_appendixes_appgroupd_">Appendices</h2><div id="chd.appa"><h3>Appendix A. Review protocols</h3><p id="chd.appa.et1"><a href="/books/NBK576823/bin/chd-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Review protocol for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</a><span class="small"> (PDF, 291K)</span></p><p id="chd.appa.et2"><a href="/books/NBK576823/bin/chd-appa-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Review protocol for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</a><span class="small"> (PDF, 276K)</span></p><p id="chd.appa.et3"><a href="/books/NBK576823/bin/chd-appa-et3.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Review protocol for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</a><span class="small"> (PDF, 290K)</span></p></div><div id="chd.appb"><h3>Appendix B. Literature search strategies</h3><div id="chd.appb.s1"><h4>Literature search strategies for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><div id="chd.appb.s1.1"><h5>Database: Medline</h5><p>Last searched on <b>Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present</b>.</p><p>Date of last search: 27 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab1"><a href="/books/NBK576823/table/chd.appb.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab1" rid-ob="figobchdappbtab1"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab1/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab1"><a href="/books/NBK576823/table/chd.appb.tab1/?report=objectonly" target="object" rid-ob="figobchdappbtab1">Table</a></h4></div></div></div><div id="chd.appb.s1.2"><h5>Database: Embase</h5><p>Last searched on <b>Embase Classic+Embase</b> 1947 to 2017 September 26.</p><p>Date of last search: 27 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab2"><a href="/books/NBK576823/table/chd.appb.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab2" rid-ob="figobchdappbtab2"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab2/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab2"><a href="/books/NBK576823/table/chd.appb.tab2/?report=objectonly" target="object" rid-ob="figobchdappbtab2">Table</a></h4></div></div></div><div id="chd.appb.s1.3"><h5>Database: Cochrane Library via Wiley Online</h5><p>Date of last search: 27 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab3"><a href="/books/NBK576823/table/chd.appb.tab3/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab3" rid-ob="figobchdappbtab3"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab3/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab3/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab3"><a href="/books/NBK576823/table/chd.appb.tab3/?report=objectonly" target="object" rid-ob="figobchdappbtab3">Table</a></h4></div></div></div></div><div id="chd.appb.s2"><h4>Literature search strategies for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><div id="chd.appb.s2.1"><h5>Database: Medline</h5><p>Last searched on <b>Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present.</b></p><p>Date of last search: 28 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab4"><a href="/books/NBK576823/table/chd.appb.tab4/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab4" rid-ob="figobchdappbtab4"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab4/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab4/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab4"><a href="/books/NBK576823/table/chd.appb.tab4/?report=objectonly" target="object" rid-ob="figobchdappbtab4">Table</a></h4></div></div></div><div id="chd.appb.s2.2"><h5>Database: Embase</h5><p>Last searched on <b>Embase Classic+Embase</b> 1947 to 2017 September 27.</p><p>Date of last search: 28 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab5"><a href="/books/NBK576823/table/chd.appb.tab5/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab5" rid-ob="figobchdappbtab5"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab5/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab5/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab5"><a href="/books/NBK576823/table/chd.appb.tab5/?report=objectonly" target="object" rid-ob="figobchdappbtab5">Table</a></h4></div></div></div><div id="chd.appb.s2.3"><h5>Database: Cochrane Library via Wiley Online</h5><p>Date of last search: 28 September 2017</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab6"><a href="/books/NBK576823/table/chd.appb.tab6/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab6" rid-ob="figobchdappbtab6"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab6/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab6/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab6"><a href="/books/NBK576823/table/chd.appb.tab6/?report=objectonly" target="object" rid-ob="figobchdappbtab6">Table</a></h4></div></div></div></div><div id="chd.appb.s3"><h4>Literature search strategies for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><div id="chd.appb.s3.1"><h5>Database: Medline & Embase (Multifile)</h5><p>Last searched on <b>Embase</b> 1974 to 2017 March 28<b>, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)</b> 1946 to Present.</p><p>Date of last search: 29 March 2017.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab7"><a href="/books/NBK576823/table/chd.appb.tab7/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab7" rid-ob="figobchdappbtab7"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab7/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab7/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab7"><a href="/books/NBK576823/table/chd.appb.tab7/?report=objectonly" target="object" rid-ob="figobchdappbtab7">Table</a></h4></div></div></div><div id="chd.appb.s3.2"><h5>Database: Cochrane Library via Wiley Online</h5><p>Date of last search: 29 March 2017.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchdappbtab8"><a href="/books/NBK576823/table/chd.appb.tab8/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figchdappbtab8" rid-ob="figobchdappbtab8"><img class="small-thumb" src="/books/NBK576823/table/chd.appb.tab8/?report=thumb" src-large="/books/NBK576823/table/chd.appb.tab8/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="chd.appb.tab8"><a href="/books/NBK576823/table/chd.appb.tab8/?report=objectonly" target="object" rid-ob="figobchdappbtab8">Table</a></h4></div></div></div></div></div><div id="chd.appc"><h3>Appendix C. Clinical evidence study selection</h3><div id="chd.appc.s1"><h4>Clinical evidence study selection for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p id="chd.appc.fig1"><a href="/books/NBK576823/figure/chd.appc.fig1/?report=objectonly" target="object" rid-ob="figobchdappcfig1" class="figpopup">Figure 1. Flow diagram of clinical article selection for duration of endocrine therapy</a></p></div><div id="chd.appc.s2"><h4>Clinical evidence study selection for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p id="chd.appc.fig2"><a href="/books/NBK576823/figure/chd.appc.fig2/?report=objectonly" target="object" rid-ob="figobchdappcfig2" class="figpopup">Figure 2. Flow diagram of clinical article selection for ovarian suppression review</a></p></div><div id="chd.appc.s3"><h4>Clinical evidence study selection for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p id="chd.appc.fig3"><a href="/books/NBK576823/figure/chd.appc.fig3/?report=objectonly" target="object" rid-ob="figobchdappcfig3" class="figpopup">Figure 3. Flow diagram of clinical article selection for chemoprevention in DCIS</a></p></div></div><div id="chd.appd"><h3>Appendix D. Clinical evidence tables</h3><div id="chd.appd.s1"><h4>Clinical evidence tables for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p id="chd.appd.et4"><a href="/books/NBK576823/bin/chd-appd-et4.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 10. Studies included in the evidence review for duration of endocrine therapy</a><span class="small"> (PDF, 524K)</span></p></div><div id="chd.appd.s2"><h4>Clinical evidence tables for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in premenopausal women with oestrogen-positive breast cancer?</h4><p id="chd.appd.et5"><a href="/books/NBK576823/bin/chd-appd-et5.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 11. Studies included in the evidence review for ovarian suppression</a><span class="small"> (PDF, 459K)</span></p></div><div id="chd.appd.s3"><h4>Clinical evidence tables for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p id="chd.appd.et6"><a href="/books/NBK576823/bin/chd-appd-et6.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 12. studies included in the evidence review for chemoprevention in DCIS</a><span class="small"> (PDF, 337K)</span></p></div></div><div id="chd.appe"><h3>Appendix E. Forest plots</h3><div id="chd.appe.s1"><h4>Forest plots for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><div id="chd.appe.s1.1"><h5>Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only</h5><p id="chd.appe.fig4"><a href="/books/NBK576823/figure/chd.appe.fig4/?report=objectonly" target="object" rid-ob="figobchdappefig4" class="figpopup">Figure 4. Disease free survival at 2.5 to 15 year follow-up</a></p><p id="chd.appe.fig5"><a href="/books/NBK576823/figure/chd.appe.fig5/?report=objectonly" target="object" rid-ob="figobchdappefig5" class="figpopup">Figure 5. Disease free survival at 2.5 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups</a></p><p id="chd.appe.fig6"><a href="/books/NBK576823/figure/chd.appe.fig6/?report=objectonly" target="object" rid-ob="figobchdappefig6" class="figpopup">Figure 6. Overall survival at 4 to 15 year follow-up</a></p><p id="chd.appe.fig7"><a href="/books/NBK576823/figure/chd.appe.fig7/?report=objectonly" target="object" rid-ob="figobchdappefig7" class="figpopup">Figure 7. Overall survival at 4 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups</a></p><p id="chd.appe.fig8"><a href="/books/NBK576823/figure/chd.appe.fig8/?report=objectonly" target="object" rid-ob="figobchdappefig8" class="figpopup">Figure 8. Compliance: did not comply with assigned treatment</a></p><p id="chd.appe.fig9"><a href="/books/NBK576823/figure/chd.appe.fig9/?report=objectonly" target="object" rid-ob="figobchdappefig9" class="figpopup">Figure 9. Treatment-related morbidity: hot flushes at 2 month to 4 year follow-up</a></p><p id="chd.appe.fig10"><a href="/books/NBK576823/figure/chd.appe.fig10/?report=objectonly" target="object" rid-ob="figobchdappefig10" class="figpopup">Figure 10. Treatment-related morbidity: secondary cancer at 5.6 to 7.6 year follow-up</a></p><p id="chd.appe.fig11"><a href="/books/NBK576823/figure/chd.appe.fig11/?report=objectonly" target="object" rid-ob="figobchdappefig11" class="figpopup">Figure 11. Treatment-related morbidity: bone fractures at 2 month to 7.6 year follow-up</a></p><p id="chd.appe.fig12"><a href="/books/NBK576823/figure/chd.appe.fig12/?report=objectonly" target="object" rid-ob="figobchdappefig12" class="figpopup">Figure 12. Treatment-related morbidity: arthralgia at 2 month to 4 year follow-up</a></p><p id="chd.appe.fig13"><a href="/books/NBK576823/figure/chd.appe.fig13/?report=objectonly" target="object" rid-ob="figobchdappefig13" class="figpopup">Figure 13. Treatment-related morbidity: cardiac disease/event at 2 month to 7.6 year follow-up</a></p><p id="chd.appe.fig14"><a href="/books/NBK576823/figure/chd.appe.fig14/?report=objectonly" target="object" rid-ob="figobchdappefig14" class="figpopup">Figure 14. Treatment-related morbidity: hypertension at 4 year follow-up</a></p><p id="chd.appe.fig15"><a href="/books/NBK576823/figure/chd.appe.fig15/?report=objectonly" target="object" rid-ob="figobchdappefig15" class="figpopup">Figure 15. Treatment-related morbidity: osteoporosis at 4 year follow-up</a></p><p id="chd.appe.fig16"><a href="/books/NBK576823/figure/chd.appe.fig16/?report=objectonly" target="object" rid-ob="figobchdappefig16" class="figpopup">Figure 16. Treatment-related morbidity: myalgia at 4 year follow-up</a></p><p id="chd.appe.fig17"><a href="/books/NBK576823/figure/chd.appe.fig17/?report=objectonly" target="object" rid-ob="figobchdappefig17" class="figpopup">Figure 17. Treatment-related morbidity: any grade 3+ toxicity at 2.5 to 5.6 year follow-up</a></p><p id="chd.appe.fig18"><a href="/books/NBK576823/figure/chd.appe.fig18/?report=objectonly" target="object" rid-ob="figobchdappefig18" class="figpopup">Figure 18. Treatment-related morbidity: vaginal dryness at 2 month to 4 year follow-up</a></p><p id="chd.appe.fig19"><a href="/books/NBK576823/figure/chd.appe.fig19/?report=objectonly" target="object" rid-ob="figobchdappefig19" class="figpopup">Figure 19. Treatment-related morbidity: vaginal bleeding at 2 month to 4 year follow-up</a></p><p id="chd.appe.fig20"><a href="/books/NBK576823/figure/chd.appe.fig20/?report=objectonly" target="object" rid-ob="figobchdappefig20" class="figpopup">Figure 20. Treatment-related morbidity: vaginal discharge at 2 month to 4 year follow-up</a></p><p id="chd.appe.fig21"><a href="/books/NBK576823/figure/chd.appe.fig21/?report=objectonly" target="object" rid-ob="figobchdappefig21" class="figpopup">Figure 21. Treatment-related morbidity: stroke at 7.6 year follow-up</a></p><p id="chd.appe.fig22"><a href="/books/NBK576823/figure/chd.appe.fig22/?report=objectonly" target="object" rid-ob="figobchdappefig22" class="figpopup">Figure 22. Treatment-related morbidity: irregular menstruation at 4 year follow-up</a></p><p id="chd.appe.fig23"><a href="/books/NBK576823/figure/chd.appe.fig23/?report=objectonly" target="object" rid-ob="figobchdappefig23" class="figpopup">Figure 23. Treatment-related morbidity: phlebitis/thromboembolic events at 2 month to 7.6 year follow-up</a></p><p id="chd.appe.fig24"><a href="/books/NBK576823/figure/chd.appe.fig24/?report=objectonly" target="object" rid-ob="figobchdappefig24" class="figpopup">Figure 24. HRQoL: change in SF-36 scores from baseline (2 year follow-up)</a></p><p id="chd.appe.fig25"><a href="/books/NBK576823/figure/chd.appe.fig25/?report=objectonly" target="object" rid-ob="figobchdappefig25" class="figpopup">Figure 25. HRQoL: change in MENQOL scores from baseline (2 year follow-up)</a></p></div></div><div id="chd.appe.s2"><h4>Forest plots for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><div id="chd.appe.s2.1"><h5>Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone</h5><p id="chd.appe.fig26"><a href="/books/NBK576823/figure/chd.appe.fig26/?report=objectonly" target="object" rid-ob="figobchdappefig26" class="figpopup">Figure 26. Overall survival at 5 to 9.9 year follow-up</a></p><p id="chd.appe.fig27"><a href="/books/NBK576823/figure/chd.appe.fig27/?report=objectonly" target="object" rid-ob="figobchdappefig27" class="figpopup">Figure 27. Disease-free survival at 5 to 9.9 year follow-up</a></p><p id="chd.appe.fig28"><a href="/books/NBK576823/figure/chd.appe.fig28/?report=objectonly" target="object" rid-ob="figobchdappefig28" class="figpopup">Figure 28. Treatment-related morbidity: vasodilation</a></p><p id="chd.appe.fig29"><a href="/books/NBK576823/figure/chd.appe.fig29/?report=objectonly" target="object" rid-ob="figobchdappefig29" class="figpopup">Figure 29. Treatment-related morbidity: weight gain</a></p><p id="chd.appe.fig30"><a href="/books/NBK576823/figure/chd.appe.fig30/?report=objectonly" target="object" rid-ob="figobchdappefig30" class="figpopup">Figure 30. Treatment-related morbidity: arthralgia</a></p><p id="chd.appe.fig31"><a href="/books/NBK576823/figure/chd.appe.fig31/?report=objectonly" target="object" rid-ob="figobchdappefig31" class="figpopup">Figure 31. Treatment-related morbidity: anxiety/depression/irritability</a></p><p id="chd.appe.fig32"><a href="/books/NBK576823/figure/chd.appe.fig32/?report=objectonly" target="object" rid-ob="figobchdappefig32" class="figpopup">Figure 32. Treatment-related morbidity: sweating</a></p><p id="chd.appe.fig33"><a href="/books/NBK576823/figure/chd.appe.fig33/?report=objectonly" target="object" rid-ob="figobchdappefig33" class="figpopup">Figure 33. Treatment-related morbidity: hot flushes (grade 3+) at 3 to 5.6 year follow-up</a></p><p id="chd.appe.fig34"><a href="/books/NBK576823/figure/chd.appe.fig34/?report=objectonly" target="object" rid-ob="figobchdappefig34" class="figpopup">Figure 34. Treatment-related morbidity: hypertension (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig35"><a href="/books/NBK576823/figure/chd.appe.fig35/?report=objectonly" target="object" rid-ob="figobchdappefig35" class="figpopup">Figure 35. Treatment-related morbidity: cardiac ischemia or infarction (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig36"><a href="/books/NBK576823/figure/chd.appe.fig36/?report=objectonly" target="object" rid-ob="figobchdappefig36" class="figpopup">Figure 36. Treatment-related morbidity: thrombosis or embolism (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig37"><a href="/books/NBK576823/figure/chd.appe.fig37/?report=objectonly" target="object" rid-ob="figobchdappefig37" class="figpopup">Figure 37. Treatment-related morbidity: musculoskeletal symptoms (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig38"><a href="/books/NBK576823/figure/chd.appe.fig38/?report=objectonly" target="object" rid-ob="figobchdappefig38" class="figpopup">Figure 38. Treatment-related morbidity: osteoporosis (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig39"><a href="/books/NBK576823/figure/chd.appe.fig39/?report=objectonly" target="object" rid-ob="figobchdappefig39" class="figpopup">Figure 39. Treatment-related morbidity: fractures (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig40"><a href="/books/NBK576823/figure/chd.appe.fig40/?report=objectonly" target="object" rid-ob="figobchdappefig40" class="figpopup">Figure 40. Treatment-related morbidity: vaginal dryness at 3 to 5.6 year follow-up</a></p><p id="chd.appe.fig41"><a href="/books/NBK576823/figure/chd.appe.fig41/?report=objectonly" target="object" rid-ob="figobchdappefig41" class="figpopup">Figure 41. Treatment-related morbidity: changes in libido at 3 to 5.6 year follow-up</a></p><p id="chd.appe.fig42"><a href="/books/NBK576823/figure/chd.appe.fig42/?report=objectonly" target="object" rid-ob="figobchdappefig42" class="figpopup">Figure 42. Treatment-related morbidity: CNS cerebrovascular ischemia (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig43"><a href="/books/NBK576823/figure/chd.appe.fig43/?report=objectonly" target="object" rid-ob="figobchdappefig43" class="figpopup">Figure 43. Treatment-related morbidity: CNS haemorrhage (grade 3+) at 5.6 year follow-up</a></p><p id="chd.appe.fig44"><a href="/books/NBK576823/figure/chd.appe.fig44/?report=objectonly" target="object" rid-ob="figobchdappefig44" class="figpopup">Figure 44. Treatment-related morbidity: vasomotor symptoms measured by Physical Symptoms and Problem List at 3 year follow-up</a></p><p id="chd.appe.fig45"><a href="/books/NBK576823/figure/chd.appe.fig45/?report=objectonly" target="object" rid-ob="figobchdappefig45" class="figpopup">Figure 45. Treatment-related morbidity: vaginal dryness measured by Physical Symptoms and Problem List at 3 year follow-up</a></p><p id="chd.appe.fig46"><a href="/books/NBK576823/figure/chd.appe.fig46/?report=objectonly" target="object" rid-ob="figobchdappefig46" class="figpopup">Figure 46. Treatment-related morbidity: changes in total body bone density (g/cm<sup>2</sup>) at 2 year follow-up</a></p><p id="chd.appe.fig47"><a href="/books/NBK576823/figure/chd.appe.fig47/?report=objectonly" target="object" rid-ob="figobchdappefig47" class="figpopup">Figure 47. Compliance: treatment completed</a></p><p id="chd.appe.fig48"><a href="/books/NBK576823/figure/chd.appe.fig48/?report=objectonly" target="object" rid-ob="figobchdappefig48" class="figpopup">Figure 48. HRQoL: FACT-G</a></p><p id="chd.appe.fig49"><a href="/books/NBK576823/figure/chd.appe.fig49/?report=objectonly" target="object" rid-ob="figobchdappefig49" class="figpopup">Figure 49. HRQoL: FACT-B</a></p></div></div><div id="chd.appe.s3"><h4>Forest plots for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><div id="chd.appe.s3.1"><h5>Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS</h5><p id="chd.appe.fig50"><a href="/books/NBK576823/figure/chd.appe.fig50/?report=objectonly" target="object" rid-ob="figobchdappefig50" class="figpopup">Figure 50. Disease-free survival at 10 year follow-up</a></p><p id="chd.appe.fig51"><a href="/books/NBK576823/figure/chd.appe.fig51/?report=objectonly" target="object" rid-ob="figobchdappefig51" class="figpopup">Figure 51. Local recurrence survival at 10 to 13.6 year follow-up</a></p><p id="chd.appe.fig52"><a href="/books/NBK576823/figure/chd.appe.fig52/?report=objectonly" target="object" rid-ob="figobchdappefig52" class="figpopup">Figure 52. Overall survival at 13.6 year follow-up</a></p><p id="chd.appe.fig53"><a href="/books/NBK576823/figure/chd.appe.fig53/?report=objectonly" target="object" rid-ob="figobchdappefig53" class="figpopup">Figure 53. Treatment-related morbidity: vaginal dryness/discharge at 3.3 to 6.2 year follow-up</a></p><p id="chd.appe.fig54"><a href="/books/NBK576823/figure/chd.appe.fig54/?report=objectonly" target="object" rid-ob="figobchdappefig54" class="figpopup">Figure 54. Treatment-related morbidity: grade 3+ toxicities at 6.2 year follow-up</a></p><p id="chd.appe.fig55"><a href="/books/NBK576823/figure/chd.appe.fig55/?report=objectonly" target="object" rid-ob="figobchdappefig55" class="figpopup">Figure 55. Treatment-related morbidity: phlebitis/thromboembolism at 6.2 year follow-up</a></p><p id="chd.appe.fig56"><a href="/books/NBK576823/figure/chd.appe.fig56/?report=objectonly" target="object" rid-ob="figobchdappefig56" class="figpopup">Figure 56. Treatment-related morbidity: mood changes at 6.2 year follow-up</a></p><p id="chd.appe.fig57"><a href="/books/NBK576823/figure/chd.appe.fig57/?report=objectonly" target="object" rid-ob="figobchdappefig57" class="figpopup">Figure 57. Treatment-related morbidity: menstrual disorders at 6.2 year follow-up</a></p><p id="chd.appe.fig58"><a href="/books/NBK576823/figure/chd.appe.fig58/?report=objectonly" target="object" rid-ob="figobchdappefig58" class="figpopup">Figure 58. Treatment-related morbidity: hot flashes at 3.3 to 6.2 year follow-up</a></p><p id="chd.appe.fig59"><a href="/books/NBK576823/figure/chd.appe.fig59/?report=objectonly" target="object" rid-ob="figobchdappefig59" class="figpopup">Figure 59. Treatment-related morbidity: fluid retention at 6.2 year follow-up</a></p><p id="chd.appe.fig60"><a href="/books/NBK576823/figure/chd.appe.fig60/?report=objectonly" target="object" rid-ob="figobchdappefig60" class="figpopup">Figure 60. Treatment-related morbidity: ocular/visual at 3.3 year follow-up</a></p><p id="chd.appe.fig61"><a href="/books/NBK576823/figure/chd.appe.fig61/?report=objectonly" target="object" rid-ob="figobchdappefig61" class="figpopup">Figure 61. Treatment-related morbidity: dermatological at 3.3 year follow-up</a></p><p id="chd.appe.fig62"><a href="/books/NBK576823/figure/chd.appe.fig62/?report=objectonly" target="object" rid-ob="figobchdappefig62" class="figpopup">Figure 62. Treatment-related morbidity: dysuria/incontinence at 3.3 year follow-up</a></p><p id="chd.appe.fig63"><a href="/books/NBK576823/figure/chd.appe.fig63/?report=objectonly" target="object" rid-ob="figobchdappefig63" class="figpopup">Figure 63. Treatment-related morbidity: vaginal bleeding at 3.3 year follow-up</a></p><p id="chd.appe.fig64"><a href="/books/NBK576823/figure/chd.appe.fig64/?report=objectonly" target="object" rid-ob="figobchdappefig64" class="figpopup">Figure 64. Treatment-related morbidity: endometrial polyps at 3.3 year follow-up</a></p><p id="chd.appe.fig65"><a href="/books/NBK576823/figure/chd.appe.fig65/?report=objectonly" target="object" rid-ob="figobchdappefig65" class="figpopup">Figure 65. Treatment-related morbidity: sweats/weight gain at 3.3 year follow-up</a></p></div></div></div><div id="chd.appf"><h3>Appendix F. GRADE tables</h3><div id="chd.appf.s1"><h4>GRADE tables for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p id="chd.appf.et7"><a href="/books/NBK576823/bin/chd-appf-et7.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 13. Clinical evidence profile: Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only</a><span class="small"> (PDF, 483K)</span></p></div><div id="chd.appf.s2"><h4>GRADE tables for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p id="chd.appf.et8"><a href="/books/NBK576823/bin/chd-appf-et8.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 14. Clinical evidence profile: Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone</a><span class="small"> (PDF, 509K)</span></p></div><div id="chd.appf.s3"><h4>GRADE tables for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p id="chd.appf.et9"><a href="/books/NBK576823/bin/chd-appf-et9.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 15. Clinical evidence profile: Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS</a><span class="small"> (PDF, 433K)</span></p></div></div><div id="chd.appg"><h3>Appendix G. Economic evidence study selection</h3><div id="chd.appg.s1"><h4>Economic evidence study selection for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for details of economic study selection.</p></div><div id="chd.appg.s2"><h4>Economic evidence study selection for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for details of economic study selection.</p></div><div id="chd.appg.s3"><h4>Economic evidence study selection for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for details of economic study selection.</p></div></div><div id="chd.apph"><h3>Appendix H. Economic evidence tables</h3><div id="chd.apph.s1"><h4>Economic evidence tables for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p id="chd.apph.et10"><a href="/books/NBK576823/bin/chd-apph-et10.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 16. Economic evidence table showing the included health economic evidence for the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer</a><span class="small"> (PDF, 330K)</span></p></div><div id="chd.apph.s2"><h4>Economic evidence tables for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in premenopausal women with oestrogen-positive breast cancer?</h4><p>No economic evidence was identified for this review question.</p></div><div id="chd.apph.s3"><h4>Economic evidence tables for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p>No economic evidence was identified for this review question.</p></div></div><div id="chd.appi"><h3>Appendix I. Health economic evidence profiles</h3><div id="chd.appi.s1"><h4>Health economic evidence profiles for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p id="chd.appi.tab1"><a href="/books/NBK576823/table/chd.appi.tab1/?report=objectonly" target="object" rid-ob="figobchdappitab1" class="figpopup">Table 17. Summary table showing the included health economic evidence for the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer</a></p></div><div id="chd.appi.s2"><h4>Health economic evidence profiles for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p>No economic evidence was identified for this review question.</p></div><div id="chd.appi.s3"><h4>Health economic evidence profiles for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p>No economic evidence was identified for this review question.</p></div></div><div id="chd.appj"><h3>Appendix J. Health economic analysis</h3><div id="chd.appj.s1"><h4>Health economic analysis for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p>No health economic analysis was carried out for this review question.</p></div><div id="chd.appj.s2"><h4>Health economic analysis for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p>No health economic analysis was carried out for this review question.</p></div><div id="chd.appj.s3"><h4>Health economic analysis for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p>No health economic analysis was carried out for this review question.</p></div></div><div id="chd.appk"><h3>Appendix K. Excluded studies</h3><div id="chd.appk.s1"><h4>Excluded studies for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><div id="chd.appk.s1.1"><h5>Clinical studies</h5><p id="chd.appk.et11"><a href="/books/NBK576823/bin/chd-appk-et11.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (308K)</span></p></div><div id="chd.appk.s1.2"><h5>Economic studies</h5><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for list of excluded economic studies.</p></div></div><div id="chd.appk.s2"><h4>Excluded studies for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><div id="chd.appk.s2.1"><h5>Clinical studies</h5><p id="chd.appk.et12"><a href="/books/NBK576823/bin/chd-appk-et12.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (420K)</span></p></div><div id="chd.appk.s2.2"><h5>Economic studies</h5><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for list of excluded economic studies.</p></div></div><div id="chd.appk.s3"><h4>Excluded studies for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><div id="chd.appk.s3.1"><h5>Clinical studies</h5><p id="chd.appk.et13"><a href="/books/NBK576823/bin/chd-appk-et13.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (337K)</span></p></div><div id="chd.appk.s3.2"><h5>Economic studies</h5><p>See <a href="/books/n/niceng101erbm1/?report=reader" class="toc-item">Supplement 1</a>: Health economics literature review for list of excluded economic studies.</p></div></div></div><div id="chd.appl"><h3>Appendix L. Research recommendations</h3><div id="chd.appl.s1"><h4>Research recommendations for 4.1. What is the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer?</h4><p>No research recommendations were made for this review question.</p></div><div id="chd.appl.s2"><h4>Research recommendations for 4.2. What is the effectiveness of ovarian suppression in addition to endocrine therapy in pre-menopausal women with oestrogen-positive breast cancer?</h4><p>No research recommendations were made for this review question.</p></div><div id="chd.appl.s3"><h4>Research recommendations for 10.4. What is the role of chemoprevention in women following initial treatment for ductal carcinoma in situ (DCIS)?</h4><p>No research recommendations were made for this review question</p></div></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Evidence reviews</p><p>developed by the National Guideline Alliance, hosted by the Royal College of Obstetricians and Gynaecologists</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2018.</div><div class="small"><span class="label">Bookshelf ID: NBK576823</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/35073001" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">35073001</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobchdtab1"><div id="chd.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab1_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_chd.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_chd.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Women (18 or over) with oestrogen-receptor positive invasive breast cancer (M0) after surgery and/or radiotherapy</td></tr><tr><th id="hd_b_chd.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_chd.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Continuous endocrine therapy for more than 5 years</td></tr><tr><th id="hd_b_chd.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_chd.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Continuous endocrine therapy for 5 years</td></tr><tr><th id="hd_b_chd.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><td headers="hd_b_chd.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Critical</b>
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<ul id="l560"><li id="lt1474" class="half_rhythm"><div>Treatment-related morbidity</div></li><li id="lt1475" class="half_rhythm"><div>Disease-free survival</div></li><li id="lt1476" class="half_rhythm"><div>Overall survival</div></li></ul>
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<b>Important</b>
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<ul id="l561"><li id="lt1477" class="half_rhythm"><div>Compliance/adherence</div></li><li id="lt1478" class="half_rhythm"><div>Treatment-related mortality</div></li><li id="lt1479" class="half_rhythm"><div>HRQoL</div></li></ul></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">HRQoL, Health-related quality of life</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab2"><div id="chd.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trial</th><th id="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional inclusion/exclusion criteria</th><th id="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interventions/comparison</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Davies 2016</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ATLAS</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l562"><li id="lt1480" class="half_rhythm"><div>Still on tamoxifen or stopped in the past year</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l563"><li id="lt1481" class="half_rhythm"><div>Intervention arm (TAM=10yrs): 20 mg of Nolvadex (tamoxifen) daily for a further 5 years (after a median of 5 years of tamoxifen prior to entry into the trial) resulting in 10 years of tamoxifen treatment.</div></li><li id="lt1482" class="half_rhythm"><div>Control arm (TAM=5yrs): no endocrine therapy (after a median of 5 years of tamoxifen prior to entry)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.1.ref3" rid="chd.s1.1.ref3">Fisher 1996</a>
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</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">B-14</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l564"><li id="lt1483" class="half_rhythm"><div>Aged ≤70 years</div></li><li id="lt1484" class="half_rhythm"><div>Node negative</div></li><li id="lt1485" class="half_rhythm"><div>No second primary cancer</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l565"><li id="lt1486" class="half_rhythm"><div>Intervention arm (TAM=10yrs): 10 mg of tamoxifen orally twice a day for 5 years (following 10mg of tamoxifen orally twice a day for 5 years during initial trial)</div></li><li id="lt1487" class="half_rhythm"><div>Control arm (TAM=5yrs): placebo twice a day for 5 years (following 10mg of tamoxifen orally twice a day for 5 years during initial trial)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.1.ref4" rid="chd.s1.1.ref4">Fisher 2001</a>
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</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">B-14</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l566"><li id="lt1488" class="half_rhythm"><div>Aged ≤70 years</div></li><li id="lt1489" class="half_rhythm"><div>Node negative</div></li><li id="lt1490" class="half_rhythm"><div>No second primary cancer</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l567"><li id="lt1491" class="half_rhythm"><div>Intervention arm (TAM=10yrs): 10 mg of tamoxifen orally twice a day for 5 years (following 10mg of tamoxifen orally twice a day for 5 years during initial trial)</div></li><li id="lt1492" class="half_rhythm"><div>Control arm (TAM=5yrs): placebo twice a day for 5 years (following 10 mg of tamoxifen orally twice a day for 5 years during initial trial)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.1.ref5" rid="chd.s1.1.ref5">Goss 2005</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MA.17</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l568"><li id="lt1493" class="half_rhythm"><div>Received prior adjuvant tamoxifen therapy for 4.5–6 years</div></li><li id="lt1494" class="half_rhythm"><div>ER and/or PR positive</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l569"><li id="lt1495" class="half_rhythm"><div>Intervention arm (ET>5yrs): 2.5 mg oral letrozole daily for 5 years (following 4.5–6 years of adjuvant tamoxifen therapy)</div></li><li id="lt1496" class="half_rhythm"><div>Control arm (ET=5yrs): placebo for 5 years (following 4.5–6 years of adjuvant tamoxifen therapy)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<a class="bibr" href="#chd.s1.1.ref7" rid="chd.s1.1.ref7">Jakesz 2007</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ABCSG 6a</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l570"><li id="lt1497" class="half_rhythm"><div>Post-menopausal</div></li><li id="lt1498" class="half_rhythm"><div>ER and/or PR positive</div></li><li id="lt1499" class="half_rhythm"><div>Stage I or stage II</div></li><li id="lt1500" class="half_rhythm"><div>Aged ≤80 years</div></li><li id="lt1501" class="half_rhythm"><div>Excluded if: previous malignant disease (except cured squamous cell skin carcinoma and early-stage cervical cancer; preoperative antineoplastic treatment and irradiation; inflammatory breast cancer; more than 4 weeks between randomisation and starting treatment; Karnofsky Index >3; bilateral oophorectomy/radiotherapy to ovaries.</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l571"><li id="lt1502" class="half_rhythm"><div>Intervention arm (ET=8yrs): 1 mg anastrozole daily for 3 years (commencing within 6 weeks of completing 5 years of adjuvant tamoxifen [4 0mg daily for 2 years followed by 20 mg daily for 3 years] during original trial ABCSG6)</div></li><li id="lt1503" class="half_rhythm"><div>Control arm (ET=5yrs): no further treatment (following 5 years of adjuvant tamoxifen [40 mg daily for 2 years followed by 20 mg daily for 3 years] during original trial ABCSG6)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.1.ref8" rid="chd.s1.1.ref8">Mamounas 2008</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">B-33</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l572"><li id="lt1504" class="half_rhythm"><div>Post-menopausal</div></li><li id="lt1505" class="half_rhythm"><div>Received tamoxifen for 57–66 months for T1–3, N0–1, M0 ER and/or PR positive invasive breast cancer</div></li><li id="lt1506" class="half_rhythm"><div>Interval between tamoxifen completion and random assignment <180 days</div></li><li id="lt1507" class="half_rhythm"><div>Excluded if inadequate hematologic, hepatic and/or renal function</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l573"><li id="lt1508" class="half_rhythm"><div>Intervention arm (ET=10yrs): exemestane for 5 years (following approximately 5 years of tamoxifen)</div></li><li id="lt1509" class="half_rhythm"><div>Control arm (ET=5yrs): placebo for 5 years (following approximately 5 years of tamoxifen)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.1.ref9" rid="chd.s1.1.ref9">Muss 2008</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MA.17</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l574"><li id="lt1510" class="half_rhythm"><div>Received prior adjuvant tamoxifen therapy for 4.5–6 years</div></li><li id="lt1511" class="half_rhythm"><div>ER and/or PR positive</div></li><li id="lt1512" class="half_rhythm"><div>Willing to complete QOL questionnaires</div></li><li id="lt1513" class="half_rhythm"><div>Fluent in English or French</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l575"><li id="lt1514" class="half_rhythm"><div>Intervention arm (ET>5yrs): 2.5 mg oral letrozole daily for 5 years (following 4.5–6 years of adjuvant tamoxifen therapy)</div></li><li id="lt1515" class="half_rhythm"><div>Control arm (ET=5yrs): placebo for 5 years (following 4.5–6 years of adjuvant tamoxifen therapy)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.1.ref11" rid="chd.s1.1.ref11">Stewart 1996</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Scottish Adjuvant Tamoxifen Trial</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l576"><li id="lt1516" class="half_rhythm"><div>Women entering the parent trial before March 1980 were ineligible, as most had already stopped tamoxifen</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l577"><li id="lt1517" class="half_rhythm"><div>Intervention arm (TAM>5yrs): 20mg tamoxifen daily to be taken indefinitely (following 5 years of tamoxifen taken during parent trial)</div></li><li id="lt1518" class="half_rhythm"><div>Control arm (TAM=5yrs): no endocrine therapy (following 5 years of tamoxifen taken during parent trial)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.1.ref12" rid="chd.s1.1.ref12">Stewart 2001</a>
|
|
</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Scottish Adjuvant Tamoxifen Trial</td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l578"><li id="lt1519" class="half_rhythm"><div>Women entering the parent trial before March 1980 were ineligible, as most had already stopped tamoxifen</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l579"><li id="lt1520" class="half_rhythm"><div>Intervention arm (TAM>5yrs): 20mg tamoxifen daily to be taken indefinitely (following 5 years of tamoxifen taken during parent trial)</div></li><li id="lt1521" class="half_rhythm"><div>Control arm (TAM=5yrs): no endocrine therapy (following 5 years of tamoxifen taken during parent trial)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey 1996</a>
|
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</td><td headers="hd_h_chd.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l580"><li id="lt1522" class="half_rhythm"><div>Tumour ≤5 cm in diameter</div></li><li id="lt1523" class="half_rhythm"><div>One or more positive axillary lymph nodes</div></li><li id="lt1524" class="half_rhythm"><div>Normal hematologic function, biochemical profiles, and bone scan</div></li></ul></td><td headers="hd_h_chd.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l581"><li id="lt1525" class="half_rhythm"><div>Intervention arm (TAM>5yrs): 10 mg tamoxifen twice daily until relapse (following 5 years of 10 mg tamoxifen twice daily and 1 year of chemotherapy [at the beginning of tamoxifen treatment] during the parent trials)</div></li><li id="lt1526" class="half_rhythm"><div>Control arm (TAM=5yrs): no endocrine therapy (following 5 years of 10mg tamoxifen twice daily and 1 year of chemotherapy [at the beginning of tamoxifen treatment] during the parent trials)</div></li></ul></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ABCSG, Austrian Breast and Colorectal Cancer Study Group; ATLAS, Adjuvant Tamoxifen Longer Against Shorter; ER, oestrogen receptor; ET, endocrine therapy; PR, progesterone receptor; QoL, quality of life; TAM, tamoxifen</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab3"><div id="chd.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Summary clinical evidence profile: Comparison 1. Endocrine therapy for greater than 5 years versus endocrine therapy for 5 years only</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab3_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_chd.tab3_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_chd.tab3_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Illustrative comparative risks* (95% CI)</th><th id="hd_h_chd.tab3_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_chd.tab3_1_1_1_3" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_chd.tab3_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_chd.tab3_1_1_1_4" style="text-align:left;vertical-align:bottom;">No of Participants (studies)</th><th id="hd_h_chd.tab3_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_chd.tab3_1_1_1_5" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th></tr><tr><th headers="hd_h_chd.tab3_1_1_1_2" id="hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assumed risk: ET=5yrs</th><th headers="hd_h_chd.tab3_1_1_1_2" id="hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Corresponding risk: ET>5yrs</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Whole sample (2.5 to 15 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.5yr DFS 93%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>2.5yr DFS 94%</p>
|
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<p>(94% to 95%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>HR 0.85</p>
|
|
<p>(0.78 to 0.93)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>16055</p>
|
|
<p>(7 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Grade 3 (5 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NR</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cannot be calculated</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>HR 0.73</p>
|
|
<p>(0.29 to 1.84)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>171</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number of events were not reported - insufficient information to judge imprecision, and therefore overall quality</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Continued tamoxifen (5.6 to 15 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.6yr DFS 67%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5.6yr DFS 69%</p>
|
|
<p>(67% to 71%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.92</p>
|
|
<p>(0.84 to 1.01)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>8480</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>2</sup><sup>,</sup><sup>3</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Switched to AI (2.5 to 5 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.5yr DFS 93%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2.5yr DFS 96%</p>
|
|
<p>(95% to 96%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.61</p>
|
|
<p>(0.5 to 0.74)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>7575</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival (4 to 15 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4yr OS 98%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>4yr OS 98%</p>
|
|
<p>(98% to 98%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.91</p>
|
|
<p>(0.83 to 1)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14555</p>
|
|
<p>(6 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>4</sup><sup>,</sup><sup>5</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival - Continued tamoxifen (5.6 to 15 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.6yr OS 89%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5.6yr OS 90%</p>
|
|
<p>(89% to 91%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.92</p>
|
|
<p>(0.84 to 1.02)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>8533</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>5</sup><sup>,</sup><sup>6</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival - Switched to AI (4 to 5 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4yr OS 98%</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>4yr OS 98%</p>
|
|
<p>(98% to 99%)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.85</p>
|
|
<p>(0.65 to 1.12)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>6022</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Compliance - did not comply with/complete assigned treatment</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">87 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>98 per 1000</p>
|
|
<p>(38 to 245)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.12</p>
|
|
<p>(0.44 to 2.81)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>19558</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>2</sup><sup>,</sup><sup>8</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - hot flushes (2 month to 4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">475 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>565 per 1000</p>
|
|
<p>(441 to 726)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.19</p>
|
|
<p>(0.93 to 1.53)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>7157</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>9</sup><sup>,</sup><sup>10</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - secondary cancer – Any (5.6 to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">125 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>126 per 1000</p>
|
|
<p>(116 to 137)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.01</p>
|
|
<p>(0.93 to 1.1)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14581</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High<sup>5</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - secondary cancer - Contralateral breast (6 to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">68 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>61 per 1000</p>
|
|
<p>(54 to 70)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.9</p>
|
|
<p>(0.79 to 1.02)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14388</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - secondary cancer – Endometrial (6 to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>18 per 1000</p>
|
|
<p>(14 to 24)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.87</p>
|
|
<p>(1.4 to 2.5)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14388</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - bone fractures (2 month to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>23 per 1000</p>
|
|
<p>(19 to 27)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.08</p>
|
|
<p>(0.9 to 1.3)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>20438</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>10</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity – arthralgia (2 month to 4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">163 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>202 per 1000</p>
|
|
<p>(184 to 223)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.24</p>
|
|
<p>(1.13 to 1.37)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>7567</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - cardiac disease/event (2 month to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>29 per 1000</p>
|
|
<p>(22 to 39)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.91</p>
|
|
<p>(0.69 to 1.19)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>18876</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity – hypertension (4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>51 per 1000</p>
|
|
<p>(40 to 64)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.01</p>
|
|
<p>(0.8 to 1.28)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5149</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>11</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity – osteoporosis (4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>82 per 1000</p>
|
|
<p>(67 to 100)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.35</p>
|
|
<p>(1.11 to 1.65)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5126</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity – myalgia (4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">120 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>148 per 1000</p>
|
|
<p>(129 to 170)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.23</p>
|
|
<p>(1.07 to 1.41)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5149</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - any grade 3+ toxicity (2.5 to 5.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">68 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>93 per 1000</p>
|
|
<p>(68 to 129)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.38</p>
|
|
<p>(1 to 1.9)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1755</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>12</sup><sup>,</sup><sup>13</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - vaginal dryness (2 month to 4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>71 per 1000</p>
|
|
<p>(48 to 104)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.34</p>
|
|
<p>(0.91 to 1.96)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>6005</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>10</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - vaginal bleeding (2 month to 4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">65 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>70 per 1000</p>
|
|
<p>(19 to 266)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.09</p>
|
|
<p>(0.29 to 4.11)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>6005</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>14</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - vaginal discharge (2 month to 4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">111 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>137 per 1000</p>
|
|
<p>(51 to 366)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.24</p>
|
|
<p>(0.46 to 3.3)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2008</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>11</sup><sup>,</sup><sup>15</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity – stroke (7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>20 per 1000</p>
|
|
<p>(16 to 26)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.09</p>
|
|
<p>(0.85 to 1.39)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>12894</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>13</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - irregular menstruation (4 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">271 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>252 per 1000</p>
|
|
<p>(206 to 303)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.93</p>
|
|
<p>(0.76 to 1.12)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1152</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>16</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - phlebitis/thromboembolic events (2 month to 7.6 year follow-up)</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3 per 1000</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>7 per 1000</p>
|
|
<p>(4 to 11)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.17</p>
|
|
<p>(1.32 to 3.57)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14902</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in SF-36 scores from baseline (2 year follow-up) - Physical health</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in SF-36 scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>1 higher</p>
|
|
<p>(0.73 lower to 2.73 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>382</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in SF-36 scores from baseline (2 year follow-up) - Mental health</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in SF-36 scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>0.6 lower</p>
|
|
<p>(2.42 lower to 1.22 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>382</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in MENQOL scores from baseline (2 year follow-up) – Vasomotor</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in MENQOL scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>0.4 higher</p>
|
|
<p>(0.15 to 0.65 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>386</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in MENQOL scores from baseline (2 year follow-up) – Psychosocial</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in MENQOL scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>0.1 lower</p>
|
|
<p>(0.31 lower to 0.11 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>379</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in MENQOL scores from baseline (2 year follow-up) – Physical</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in MENQOL scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>0 higher</p>
|
|
<p>(0.21 lower to 0.21 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>386</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL - change in MENQOL scores from baseline (2 year follow-up) - Sexual</td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_2 hd_h_chd.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL - change in MENQOL scores from baseline (2 year follow-up) - physical health in the intervention groups was</p>
|
|
<p>0.2 higher</p>
|
|
<p>(0.08 lower to 0.48 higher)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>263</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Rates of disease-free survival and overall survival in the control group correspond to the trial with the shortest follow-up period</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AI, aromatase inhibitor; CI: Confidence interval; DFS: disease-free survival; ET, endocrine therapy; HRQoL: health-related quality of life; MENQOL, menopause-specific quality of life; NR: Not reported; OS, overall survival; RR: Risk ratio; SF-36, 36-Item Short Form Survey</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="chd.tab3_1"><p class="no_margin">Significant heterogeneity - I squared value 82% - heterogeneity explored in subgroup analyses</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="chd.tab3_2"><p class="no_margin">Serious indirectness in Scottish Adjuvant Tamoxifen Trial due to population; however, this study does not have very much weight in the analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="chd.tab3_3"><p class="no_margin">Significant heterogeneity - I squared value 85% - not possible to further investigate heterogeneity as subgroups of interest identified by the GC were not reported for trials that contributed to this estimate</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="chd.tab3_4"><p class="no_margin">Significant heterogeneity - I squared value 53% - heterogeneity explored in subgroup analyses</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="chd.tab3_5"><p class="no_margin">Serious indirectness in Scottish Adjuvant Tamoxifen Trial and <a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey 1996</a> due to population; however, neither of these studies have much weight in the analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="chd.tab3_6"><p class="no_margin">Significant heterogeneity - I squared value 71% - not possible to further investigate heterogeneity as subgroups of interest identified by the GC were not reported for trials that contributed to this estimate</p></div></dd></dl><dl class="bkr_refwrap"><dt>7</dt><dd><div id="chd.tab3_7"><p class="no_margin"><300 events</p></div></dd></dl><dl class="bkr_refwrap"><dt>8</dt><dd><div id="chd.tab3_8"><p class="no_margin">Significant heterogeneity - I squared value 99%. High rates of unexplained heterogeneity as subgroups of interest were only identified by the GC for critical outcomes.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9</dt><dd><div id="chd.tab3_9"><p class="no_margin">Random effects model with significant heterogeneity - I squared value 91% high rates of unexplained heterogeneity as subgroups of interest were only identified by the GC for critical outcomes.</p></div></dd></dl><dl class="bkr_refwrap"><dt>10</dt><dd><div id="chd.tab3_10"><p class="no_margin">95% CI crosses both no effect (1) and GRADE default value for minimally important difference (1.25)</p></div></dd></dl><dl class="bkr_refwrap"><dt>11</dt><dd><div id="chd.tab3_11"><p class="no_margin"><300 events and 95% CI crosses both boundaries for no effect (1) and minimally important differences (0.8 and 1.25) based on GRADE default values</p></div></dd></dl><dl class="bkr_refwrap"><dt>12</dt><dd><div id="chd.tab3_12"><p class="no_margin">Serious indirectness in <a class="bibr" href="#chd.s1.1.ref13" rid="chd.s1.1.ref13">Tormey 1996</a> due to population but study does not have much weight in the analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>13</dt><dd><div id="chd.tab3_13"><p class="no_margin"><300 events and 95% crosses both no effect (1) and minimally important difference (1.25) based on GRADE default value</p></div></dd></dl><dl class="bkr_refwrap"><dt>14</dt><dd><div id="chd.tab3_14"><p class="no_margin">95% CI crosses both boundaries for no effect (1) and minimally important differences (0.8 and 1.25) based on GRADE default values</p></div></dd></dl><dl class="bkr_refwrap"><dt>15</dt><dd><div id="chd.tab3_15"><p class="no_margin">Significant heterogeneity - I squared value 87% - high rates of unexplained heterogeneity as subgroups of interest were only identified by the GC for critical outcomes.</p></div></dd></dl><dl class="bkr_refwrap"><dt>16</dt><dd><div id="chd.tab3_16"><p class="no_margin">95% CI crosses both no effect (1) and minimally important difference (0.8) based on GRADE default value See <a href="#chd.appf">appendix F</a> for full GRADE tables.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab4"><div id="chd.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab4_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_chd.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_chd.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pre-menopausal adult women (18 or over) with oestrogen-receptor positive invasive breast cancer.</td></tr><tr><th id="hd_b_chd.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_chd.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Endocrine therapy with ovarian suppression:
|
|
<ul id="l590"><li id="lt1558" class="half_rhythm"><div>Luteinizing-hormone releasing hormone (LHRH) agonists</div></li><li id="lt1559" class="half_rhythm"><div>Oophorectomy</div></li></ul></td></tr><tr><th id="hd_b_chd.tab4_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_chd.tab4_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Endocrine therapy without ovarian suppression.</td></tr><tr><th id="hd_b_chd.tab4_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><td headers="hd_b_chd.tab4_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Critical</b>
|
|
<ul id="l591"><li id="lt1560" class="half_rhythm"><div>Disease-free survival</div></li><li id="lt1561" class="half_rhythm"><div>Treatment-related morbidity</div></li><li id="lt1562" class="half_rhythm"><div>HRQoL</div></li></ul>
|
|
<b>Important</b>
|
|
<ul id="l592"><li id="lt1563" class="half_rhythm"><div>Local recurrence rate</div></li><li id="lt1564" class="half_rhythm"><div>Overall survival</div></li><li id="lt1565" class="half_rhythm"><div>Compliance</div></li><li id="lt1566" class="half_rhythm"><div>Treatment-related mortality</div></li></ul></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">HRQoL, Health-related quality of life; LHRH, Luteinizing-hormone releasing hormone</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab5"><div id="chd.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">Summary of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Trial</th><th id="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Additional inclusion/exclusion criteria</th><th id="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Interventions/comparison</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a class="bibr" href="#chd.s1.2.ref1" rid="chd.s1.2.ref1">Adjuvant Breast Cancer Trials Collaborative Group 2007</a>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ABC Ovarian Ablation or Suppression</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<p>No previous malignancy (except cervical cancer in situ or basal cell carcinoma)</p>
|
|
<p>No previous systematic therapy for their current breast cancer</p>
|
|
<p>Included patients receiving chemotherapy</p>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Intervention arm (TAM+OFS): 20 mg/day tamoxifen for 5 years and either oophorectomy, ovarian radiation, goserelin at 3.6 mg or leuprorelin acetate at 3.75 mg every 28 days for at least 2 years.</p>
|
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<p>Control arm (TAM): 20mg/day tamoxifen for 5 years</p>
|
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</td></tr><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a class="bibr" href="#chd.s1.2.ref3" rid="chd.s1.2.ref3">Baum 2006</a>
|
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</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ZIPP</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Normal liver function, renal function and full blood count</p>
|
|
<p>No hormonal therapy in 6 weeks prior to joining trial</p>
|
|
<p>No previous treatment for malignancies except for basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix.</p>
|
|
<p>Excluded if unfit for surgery, severely limited life expectancy, primary carcinoma fixed to underlying muscle/chest wall or was ulcerated, had skin infiltration or axillary nodes that demonstrated deep fixity; unwilling/unable to attend treatment and long-term follow-up Included patients receiving chemotherapy</p>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intervention arm (TAM+GOS): Oral tamoxifen (20 or 40 mg daily) and goserelin 3.6 mg subcutaneous injection into abdominal wall.</p>
|
|
<p>Control arm (TAM): Oral tamoxifen (20 or 40 mg daily</p>
|
|
</td></tr><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.2.ref5" rid="chd.s1.2.ref5">Francis 2015</a>
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</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SOFT</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Patients had to have undergone either a total mastectomy with subsequent optional radiotherapy or breast-conserving surgery with subsequent radiotherapy. Either axillary dissection or a sentinel-node biopsy was required</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Intervention arm (TAM + OFS): Oral tamoxifen at a dose of 20 mg daily and ovarian suppression by triptorelin at a dose of 3.75 mg administered by means of intramuscular injection every 28 days, bilateral oophorectomy, or bilateral ovarian irradiation. Treatment duration 5 years.</p>
|
|
<p>Control arm (TAM): Oral tamoxifen at a dose of 20 mg daily for five years.</p>
|
|
</td></tr><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a class="bibr" href="#chd.s1.2.ref6" rid="chd.s1.2.ref6">Nystedt 2003</a>
|
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</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ZIPP</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post primary surgery Included patients receiving chemotherapy (but able to extract data separately for those not receiving chemotherapy)</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years of endocrine therapy in both groups; details not reported (see <a class="bibr" href="#chd.s1.2.ref3" rid="chd.s1.2.ref3">Baum 2006</a>)</td></tr><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#chd.s1.2.ref9" rid="chd.s1.2.ref9">Sverrisdottir 2004</a>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ZIPP</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Primary surgery consisting of a mastectomy or lumpectomy plus axillary node dissection Histopathologic tumour size greater than 10 mm</p>
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<p>Exclusion criteria: inoperable breast cancer, prior radiotherapy or neoadjuvant chemotherapy, and prior or concurrent endocrine therapy</p>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intervention arm (TAM+GOS): tamoxifen 40 mg/d orally and goserelin 3.6 mg subcutaneously every 28 days. The treatment duration for both tamoxifen and goserelin was 2 years.</p>
|
|
<p>Control arm (TAM): tamoxifen 40 mg/d orally for two years.</p>
|
|
</td></tr><tr><td headers="hd_h_chd.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a class="bibr" href="#chd.s1.2.ref10" rid="chd.s1.2.ref10">Tevaarwerk 2014</a>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">E-3193</td><td headers="hd_h_chd.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Node-negative Tumours ≤3 cm in diameter No prior systemic therapy (except ≤12 weeks of tamoxifen).</p>
|
|
<p>No locally advanced disease.</p>
|
|
<p>Other adjuvant systemic therapies including chemotherapy were not permitted.</p>
|
|
</td><td headers="hd_h_chd.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intervention arm (TAM + OFS): 20 mg oral tamoxifen per day for 5 years. OFS by LHRH analog goserelin 3.6 mg depot every 4 weeks for 5 years, LHRH analog leuprolide acetate 3.75 mg every 4 weeks for 5 years, surgical ablation, or 4) ovarian ablation radiation (20gy in 10 fractions). No dose reductions permitted</p>
|
|
<p>Control arm (TAM): 20 mg oral tamoxifen per day for 5 years</p>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ABC, adjuvant breast cancer; GOS, goserelin; LHRH, Luteinizing-hormone releasing hormone; OFS, ovarian function suppression; SOFT, suppression of ovarian function trial; TAM, tamoxifen; ZIPP, Zoladex in pre-menopausal patients trial</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab6"><div id="chd.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">Summary clinical evidence profile: Comparison 1. Ovarian suppression plus tamoxifen versus tamoxifen alone</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab6_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab6_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_chd.tab6_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_chd.tab6_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Illustrative comparative risks* (95% CI)</th><th id="hd_h_chd.tab6_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_chd.tab6_1_1_1_3" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_chd.tab6_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_chd.tab6_1_1_1_4" style="text-align:left;vertical-align:bottom;">No of Participants (studies)</th><th id="hd_h_chd.tab6_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_chd.tab6_1_1_1_5" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th></tr><tr><th headers="hd_h_chd.tab6_1_1_1_2" id="hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assumed risk: Tamoxifen alone<sup>6</sup></th><th headers="hd_h_chd.tab6_1_1_1_2" id="hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Corresponding risk: Tamoxifen + ovarian suppression</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival - Whole sample (5 to 9.9 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr OS 95%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>5 yr OS 96%</p>
|
|
<p>[95% to 97%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.81</p>
|
|
<p>(0.66 to 1)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>4108</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival - Previous chemotherapy: yes (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr OS 91%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr OS 94%</p>
|
|
<p>[91% to 96%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.64</p>
|
|
<p>(0.42 to 0.97)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1084</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival - Previous chemotherapy: no (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr OS 100%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr OS 99%</p>
|
|
<p>[96% to 100%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 3.84</p>
|
|
<p>(0.81 to 18.18)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>949</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Whole sample (5 to 9.9 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 85%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 87%</p>
|
|
<p>[84% to 89%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.83</p>
|
|
<p>(0.67 to 1.03)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2370</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Age: <35 (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 67%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 76%</p>
|
|
<p>[64% to 85%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.68</p>
|
|
<p>(0.42 to 1.11)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>233</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Age: 35–39 (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 80%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 84%</p>
|
|
<p>[76% to 90%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.78</p>
|
|
<p>(0.49 to 1.24)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>387</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Age: 40+ (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 92%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 93%</p>
|
|
<p>(91% to 95%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.9</p>
|
|
<p>(0.66 to 1.22)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1413</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Grade: 1 (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 94%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 92%</p>
|
|
<p>(86% to 96%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 1.23</p>
|
|
<p>(0.66 to 2.29)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>540</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Grade: 2 (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 84%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 89%</p>
|
|
<p>(85% to 92%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.67</p>
|
|
<p>(0.48 to 0.94)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1006</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Grade: 3 (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 74%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 77%</p>
|
|
<p>(68% to 83%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.85</p>
|
|
<p>(0.59 to 1.23)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>439</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - HER2: negative (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 85%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 87%</p>
|
|
<p>(84% to 90%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.88</p>
|
|
<p>(0.69 to 1.13)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1724</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - HER2: positive (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 76%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 89%</p>
|
|
<p>(80% to 94%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.42</p>
|
|
<p>(0.22 to 0.8)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>236</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Previous chemotherapy: yes (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 77%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 81%</p>
|
|
<p>(76% to 85%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.82</p>
|
|
<p>(0.63 to 1.06)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1084</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Previous chemotherapy: no (5 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 yr DFS 93%</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5 yr DFS 94%</p>
|
|
<p>(91% to 96%)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.83</p>
|
|
<p>(0.52 to 1.33)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>949</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: vasodilation (follow-up not-reported)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">168 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>438 per 1000</p>
|
|
<p>(349 to 549)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.6</p>
|
|
<p>(2.07 to 3.26)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>920</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: weight gain (follow-up not reported)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>89 per 1000</p>
|
|
<p>(60 to 133)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.57</p>
|
|
<p>(1.05 to 2.35)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1265</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: arthralgia (follow-up not-reported)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>24 per 1000</p>
|
|
<p>(8 to 75)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.79</p>
|
|
<p>(0.89 to 8.69)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>920</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: anxiety/depression/irritability (follow-up not reported)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>48 per 1000</p>
|
|
<p>(26 to 87)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.5</p>
|
|
<p>(0.82 to 2.75)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3276</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: sweating (follow-up not reported)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>35 per 1000</p>
|
|
<p>(14 to 89)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 4.49</p>
|
|
<p>(1.79 to 11.24)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1265</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: hot flushes (grade 3+; 3 to 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">71 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>159 per 1000</p>
|
|
<p>(84 to 300)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.23</p>
|
|
<p>(1.18 to 4.21)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2356</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: hypertension (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>75 per 1000</p>
|
|
<p>(53 to 105)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.39</p>
|
|
<p>(0.99 to 1.95)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: cardiac ischemia or infarction (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1 per 1000</p>
|
|
<p>(0 to 9)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.25</p>
|
|
<p>(0.03 to 2.24)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: thrombosis or embolism (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>17 per 1000</p>
|
|
<p>(9 to 33)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1</p>
|
|
<p>(0.51 to 1.95)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: musculoskeletal symptoms (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>54 per 1000</p>
|
|
<p>(39 to 78)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.87</p>
|
|
<p>(0.62 to 1.24)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: osteoporosis (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3 per 1000</p>
|
|
<p>(0 to 29)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 3</p>
|
|
<p>(0.31 to 28.82)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: fractures (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>8 per 1000</p>
|
|
<p>(3 to 21)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1</p>
|
|
<p>(0.38 to 2.66)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: vaginal dryness (3 to 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">358 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>426 per 1000</p>
|
|
<p>(386 to 469)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.19</p>
|
|
<p>(1.08 to 1.31)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2356</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: changes in libido (3 to 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">363 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>406 per 1000</p>
|
|
<p>(370 to 446)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.12</p>
|
|
<p>(1.02 to 1.23)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2356</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: CNS cerebrovascular ischemia (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1 per 1000</p>
|
|
<p>(0 to 9)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.25</p>
|
|
<p>(0.03 to 2.24)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>1</sup><sup>,</sup><sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment related morbidity: CNS haemorrhage (grade 3+; 5.6 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>0 per 1000</p>
|
|
<p>(0 to 0)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 3</p>
|
|
<p>(0.12 to 73.63)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2011</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: vasomotor symptoms measured by Physical Symptoms and Problem List (3 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean treatment-related morbidity: vasomotor symptoms measured by Physical Symptoms and Problem List in the intervention groups was</p>
|
|
<p>0.1 higher</p>
|
|
<p>(0.44 lower to 0.64 higher)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>60</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity: vaginal dryness measured by Physical Symptoms and Problem List (3 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;"></td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean treatment-related morbidity: vaginal dryness measured by Physical Symptoms and Problem List in the intervention groups was</p>
|
|
<p>0.17 lower</p>
|
|
<p>(0.5 lower to 0.16 higher)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;"></td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>63</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Changes in total body bone density (g/cm2; 2 year follow-up)</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean changes in total body bone density (g/cm2) in the intervention groups was</p>
|
|
<p>0 higher</p>
|
|
<p>(0.01 lower to 0.02 higher)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>32</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Compliance: treatment completed</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">407 per 1000</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>452 per 1000</p>
|
|
<p>(354 to 578)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.11</p>
|
|
<p>(0.87 to 1.42)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>337</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL: FACT-G</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;"></td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL: FACT-G in the intervention groups was</p>
|
|
<p>1.42 lower</p>
|
|
<p>(5.06 lower to 2.22 higher)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;"></td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>188</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>1</sup><sup>,</sup><sup>4</sup></td></tr><tr><td headers="hd_h_chd.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRQoL: FACT-B</td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_2 hd_h_chd.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean HRQoL: FACT-B in the intervention groups was</p>
|
|
<p>0.8 lower</p>
|
|
<p>(5.66 lower to 4.06 higher)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>177</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup><sup>,</sup><sup>5</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Rates of disease-free survival and overall survival in the control group correspond to the trial with the shortest follow-up period</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CNS, central nervous system; CI: Confidence interval; DFS, disease-free survival; FACT-B Functional assessment of cancer therapy – breast cancer; FACT-G Functional assessment of cancer therapy – general; HR: Hazard ratio; OS, overall survival; RR: Risk ratio;</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="chd.tab6_1"><p class="no_margin">Unclear allocation concealment and/or randomisation sequence generation</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="chd.tab6_2"><p class="no_margin">Optimal information size not met (Number of events=300 for dichotomous outcomes, N=400 for continuous outcomes</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="chd.tab6_3"><p class="no_margin">29% of TAM+GOS arm and 11% of TAM arm were ER negative (Swedish subgroup of ZIPP trial)</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="chd.tab6_4"><p class="no_margin">MID for FACT-G was 3 points; N<400</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="chd.tab6_5"><p class="no_margin">MID for FACT-B total score was 7 points</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="chd.tab6_6"><p class="no_margin">Tamoxifen only group illustrative 5 year survival values come from the relevant subgroups in the SOFT trial</p></div></dd></dl><dl class="bkr_refwrap"><dt>7</dt><dd><div id="chd.tab6_7"><p class="no_margin">Patients in the ZIPP and ABC trials received concurrent chemotherapy, at similar rates in both arms</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab7"><div id="chd.tab7" class="table"><h3><span class="label">Table 7</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab7_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_chd.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_chd.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adults (18 or over) with DCIS who have undergone initial surgery</td></tr><tr><th id="hd_b_chd.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_chd.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l600"><li id="lt1605" class="half_rhythm"><div>Aromatase inhibitors (e.g., anastrozole, exemestane, letrozole)</div></li><li id="lt1606" class="half_rhythm"><div>Tamoxifen</div></li><li id="lt1607" class="half_rhythm"><div>Raloxifene</div></li></ul></td></tr><tr><th id="hd_b_chd.tab7_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_chd.tab7_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No treatment</td></tr><tr><th id="hd_b_chd.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><td headers="hd_b_chd.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Critical</b>
|
|
<ul id="l601"><li id="lt1608" class="half_rhythm"><div>Disease-free survival</div></li><li id="lt1609" class="half_rhythm"><div>Local recurrence</div></li><li id="lt1610" class="half_rhythm"><div>Treatment-related morbidity</div></li></ul>
|
|
<b>Important</b>
|
|
<ul id="l602"><li id="lt1611" class="half_rhythm"><div>HRQoL</div></li><li id="lt1612" class="half_rhythm"><div>Overall survival</div></li><li id="lt1613" class="half_rhythm"><div>Treatment adherence</div></li></ul></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">HRQoL, health-related quality of life</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab8"><div id="chd.tab8" class="table"><h3><span class="label">Table 8</span><span class="title">Summary of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab8_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_chd.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trial</th><th id="hd_h_chd.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional inclusion/exclusion criteria</th><th id="hd_h_chd.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interventions/comparison</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.3.ref1" rid="chd.s1.3.ref1">Cuzick 2011</a>
|
|
</td><td headers="hd_h_chd.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">UK/ANZ</td><td headers="hd_h_chd.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l603"><li id="lt1614" class="half_rhythm"><div>Unilateral or bilateral DCIS that could be excised with clear margins by breast conserving surgery</div></li></ul></td><td headers="hd_h_chd.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l604"><li id="lt1615" class="half_rhythm"><div>Intervention arm (TAM): 20mg tamoxifen daily for 5 years; radiotherapy was administered in 25 fractions over 5 weeks (2Gy given 5 times a week; total 50Gy)</div></li><li id="lt1616" class="half_rhythm"><div>Control arm (No chemoprevention): radiotherapy was administered in 25 fractions over 5 weeks (2Gy given 5 times a week; total 50Gy)</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.3.ref3" rid="chd.s1.3.ref3">Fisher 1999</a>
|
|
</td><td headers="hd_h_chd.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NSABP-B34</td><td headers="hd_h_chd.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l605"><li id="lt1617" class="half_rhythm"><div>Women with DCIS with a life expectancy of at least 10 years. Axillary dissection (if done) had to show negative lymph node involvement and time between surgery and randomisation ≤56 days.</div></li><li id="lt1618" class="half_rhythm"><div>Exclusion: previous diagnosis of cancer (except in situ carcinoma of the cervix or squamous cell or basal-cell carcinoma of the skin)</div></li></ul></td><td headers="hd_h_chd.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l606"><li id="lt1619" class="half_rhythm"><div>Intervention arm (TAM): lumpectomy was performed within 56 days of randomisation. Radiation therapy total of 50 Gy. 10 mg tamoxifen was taken twice daily for 5 years.</div></li><li id="lt1620" class="half_rhythm"><div>Control arm (No chemoprevention): lumpectomy was performed within 56 days of randomisation. Radiation therapy total of 50 Gy. Placebo was taken twice daily for 5 years</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.3.ref4" rid="chd.s1.3.ref4">Guerrieri-Gonzaga 2006</a>
|
|
</td><td headers="hd_h_chd.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_chd.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l607"><li id="lt1621" class="half_rhythm"><div>Premenopausal women with: 1) in situ cancer or small invasive cancer of favourable prognosis within the last 3 years, or 2) Gail 5-year risk for breast cancer of 1.3%.</div></li><li id="lt1622" class="half_rhythm"><div>Exclusion: prior chemotherapy or hormonal therapy; malignancy other than carcinoma-in-situ and skin basal cell carcinoma; retinal/ocular disorders; photodermatitis; stage III or IV endometriosis; grade 2 alterations of hematologic, liver and renal function; hypertriglyceridemia; CNS diseases; major psychiatric diseases; history of venous thromboembolism; transient ischemic attack.</div></li></ul></td><td headers="hd_h_chd.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l608"><li id="lt1623" class="half_rhythm"><div>Intervention arm (TAM): 5 mg tamoxifen and fenretinide placebo capsules daily for 2 years</div></li><li id="lt1624" class="half_rhythm"><div>Control arm (No chemoprevention): tamoxifen and fenretinide placebo capsules daily for 2 years</div></li></ul></td></tr><tr><td headers="hd_h_chd.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#chd.s1.3.ref6" rid="chd.s1.3.ref6">Wapnir 2011</a>
|
|
</td><td headers="hd_h_chd.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NSAPB-B34</td><td headers="hd_h_chd.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l609"><li id="lt1625" class="half_rhythm"><div>Inclusion criteria</div></li><li id="lt1626" class="half_rhythm"><div>Women with DCIS with a life expectancy of at least 10 years. Axillary dissection (if done) had to show negative lymph node involvement and time between surgery and randomisation ≤56 days</div></li><li id="lt1627" class="half_rhythm"><div>Exclusion: previous diagnosis of cancer (except in situ carcinoma of the cervix or squamous cell or basal-cell carcinoma of the skin)</div></li></ul></td><td headers="hd_h_chd.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="l610"><li id="lt1628" class="half_rhythm"><div>Intervention arm (TAM): Radiation started within 8 weeks of surgery and was given at 10Gy per week over 5 weeks (total 50Gy); optional boost of 10Gy to lumpectomy cavity. 10mg tamoxifen taken twice daily for 5 years</div></li><li id="lt1629" class="half_rhythm"><div>Control arm (No chemoprevention): Radiation started within 8 weeks of surgery and was given at 10Gy per week over 5 weeks (total 50Gy); optional boost of 10Gy to lumpectomy cavity. Placebo was taken twice daily for 5 years</div></li></ul></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CNS, central nervous system; DCIS, ductal carcinoma in situ; Gy, gray; NSABP, National Surgical Adjuvant Breast and Bowel Project; TAM, tamoxifen; UK/ANZ, United Kingdom, Australia and New Zealand</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdtab9"><div id="chd.tab9" class="table"><h3><span class="label">Table 9</span><span class="title">Summary clinical evidence profile: Comparison 1. Tamoxifen versus no chemoprevention for people with excised DCIS</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.tab9/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.tab9_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd.tab9_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_chd.tab9_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_chd.tab9_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Illustrative comparative risks* (95% CI)</th><th id="hd_h_chd.tab9_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_chd.tab9_1_1_1_3" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_chd.tab9_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_chd.tab9_1_1_1_4" style="text-align:left;vertical-align:bottom;">No of Participants (studies)</th><th id="hd_h_chd.tab9_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_chd.tab9_1_1_1_5" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th></tr><tr><th headers="hd_h_chd.tab9_1_1_1_2" id="hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assumed risk: No chemoprevention</th><th headers="hd_h_chd.tab9_1_1_1_2" id="hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Corresponding risk: Tamoxifen</th></tr></thead><tbody><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - Whole sample (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10yr DFS 74%</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>10yr DFS 81%</p>
|
|
<p>(77% to 84%)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.71</p>
|
|
<p>(0.58 to 0.87)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1576</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - BCS+RT (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10yr DFS 87%</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>10yr DFS 87%</p>
|
|
<p>(80% to 92%)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.99</p>
|
|
<p>(0.61 to 1.60)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>523</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Disease-free survival - BCS-RT (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10yr DFS 68%</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>10yr DFS 76%</p>
|
|
<p>(71% to 80%)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.71</p>
|
|
<p>(0.57 to 0.88)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1053</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Local recurrence – Mixed (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">79% free from local recurrence at 10 yrs</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">83% free from local recurrence at 10 yrs (79% to 86%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.78</p>
|
|
<p>(0.62 to 0.99)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1576</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Local recurrence – Invasive (13.6 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">91% free from local recurrence at 13.6 yrs</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">94% free from local recurrence at 13.6 yrs (91% to 96%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.68</p>
|
|
<p>(0.49 to 0.95)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1799</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Local recurrence – DCIS (13.6yr follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">92% free from local recurrence at 13.6 yrs</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">93% free from local recurrence at 13.6 yrs (91% to 95%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.84</p>
|
|
<p>(0.60 to 1.18)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1799</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Local recurrence - BCS+RT (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">91% free from local recurrence at 10 yrs</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">92% free from local recurrence at 10 yrs (85% to 95%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.93</p>
|
|
<p>(0.50 to 1.74)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>523</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Local recurrence - BCSRT (10 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">74% free from local recurrence at 10 yrs</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">79% free from local recurrence at 10 yrs (74% to 84%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.77</p>
|
|
<p>(0.60 to 0.99)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1053</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Overall survival (13.6 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.6yr OS 95%</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.6yr OS 96% (94% to 97%)</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HR 0.86</p>
|
|
<p>(0.66 to 1.12)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1799</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>1</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - vaginal dryness/discharge (3.3 to 6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">198 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>321 per 1000</p>
|
|
<p>(274 to 375)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.62</p>
|
|
<p>(1.38 to 1.89)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1897</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - grade 3+ toxicities (6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>54 per 1000</p>
|
|
<p>(35 to 82)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.26</p>
|
|
<p>(0.83 to 1.91)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1781</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>3</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - phlebitis/thromboembolis m (6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>18 per 1000</p>
|
|
<p>(7 to 43)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.28</p>
|
|
<p>(0.94 to 5.52)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1781</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>3</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - mood changes (6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">107 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>106 per 1000</p>
|
|
<p>(80 to 138)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.99</p>
|
|
<p>(0.75 to 1.29)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1781</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low<sup>4</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - menstrual disorders (6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">160 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>191 per 1000</p>
|
|
<p>(156 to 235)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.2</p>
|
|
<p>(0.98 to 1.47)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1781</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>5</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - hot flashes (3.3 to 6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">568 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>670 per 1000</p>
|
|
<p>(624 to 715)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.18</p>
|
|
<p>(1.1 to 1.26)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1897</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High<sup>2</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - fluid retention (6.2 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">279 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>326 per 1000</p>
|
|
<p>(284 to 376)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.17</p>
|
|
<p>(1.02 to 1.35)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1781</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High</td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - ocular/visual (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">431 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>328 per 1000</p>
|
|
<p>(203 to 526)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.76</p>
|
|
<p>(0.47 to 1.22)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>6</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - dermatology/skin (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">431 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>293 per 1000</p>
|
|
<p>(177 to 483)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.68</p>
|
|
<p>(0.41 to 1.12)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>6</sup><sup>,</sup><sup>7</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - dysuria/incontinence (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">86 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>86 per 1000</p>
|
|
<p>(27 to 282)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1</p>
|
|
<p>(0.31 to 3.27)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>4</sup><sup>,</sup><sup>6</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - vaginal bleeding (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">69 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>121 per 1000</p>
|
|
<p>(37 to 390)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.75</p>
|
|
<p>(0.54 to 5.66)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>4</sup><sup>,</sup><sup>6</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - endometrial polyps (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>69 per 1000</p>
|
|
<p>(16 to 295)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.33</p>
|
|
<p>(0.31 to 5.7)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>4</sup><sup>,</sup><sup>6</sup></td></tr><tr><td headers="hd_h_chd.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment-related morbidity - sweats/weight gain (3.3 year follow-up)</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">138 per 1000</td><td headers="hd_h_chd.tab9_1_1_1_2 hd_h_chd.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>156 per 1000</p>
|
|
<p>(65 to 374)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.13</p>
|
|
<p>(0.47 to 2.71)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>116</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_chd.tab9_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low<sup>4</sup><sup>,</sup><sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Rates of disease-free survival, local recurrence and overall survival in the control group correspond to the trial with the shortest follow-up period</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">BCS: breast-conserving surgery; CI: Confidence interval; DFS, disease-free survival; HR: hazards ratio; OS, overall survival; RR: Risk ratio; RT: radiotherapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="chd.tab9_1"><p class="no_margin"><300 events</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="chd.tab9_2"><p class="no_margin">Very serious indirectness in Guerrieri-Gonzaga 2006 due to population; evidence not downgraded as study only given 4.9% weight in analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="chd.tab9_3"><p class="no_margin"><300 events; 95% CI crosses boundary of no effect (1) and minimally important difference (1.25) based on GRADE default values</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="chd.tab9_4"><p class="no_margin"><300 events; 95% CI crosses both boundary for no effect (1) and minimally important differences (0.8 and 1.25) based on GRADE default values</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="chd.tab9_5"><p class="no_margin">95% CI crosses boundary of no effect (1) and minimally important difference (1.25) based on GRADE default values</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="chd.tab9_6"><p class="no_margin">Only 57% of population had excised DCIS</p></div></dd></dl><dl class="bkr_refwrap"><dt>7</dt><dd><div id="chd.tab9_7"><p class="no_margin"><300 events; 95% CI crosses boundary of no effect (1) and minimally important difference (0.8) based on GRADE default values</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchdappbtab1"><div id="chd.appb.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast Neoplasms/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Neoplasms, Ductal, Lobular, and Medullary”/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Intraductal, Noninfiltrating/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Lobular/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Medullary/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 or 2 or 3 or 4 or 5</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 or 8</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj milk).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj tender$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 or 11</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 not 12</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Neoplasms/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13 and 14</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Paget’s Disease, Mammary/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget$ and (breast$ or mammary or nipple$)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17 or 18 or 19</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 or 20</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Aromatase Inhibitors/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromatase inhibitor$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">anastrazole.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">arimidex.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letrozole.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">femara.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exemestane.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromasin.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tamoxifen/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Nolvadex or tamoxifen$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/22-31</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 32</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Time Factors/</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(duration$ or timing).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(sequenc$ or sequential).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">extended.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(continu$ or stop$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((optimal or different) adj (regimen$ or treatment or therapy or course)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(length adj2 (regimen$ or treatment or therapy or course)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/34-40</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33 and 41</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(“MA.17” or MA17 or ATTOM or ATLAS).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 43</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42 or 44</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 45 to yr=“1996 -Current”</td></tr><tr><td headers="hd_h_chd.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_chd.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Limit 46 to RCTs and SRs, and general exclusions filter applied</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab2"><div id="chd.appb.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast cancer/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp medullary carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp intraductal carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast tumor/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 or 2 or 3 or 4 or 5</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 or 8</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj milk).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj tender$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 or 11</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 not 12</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp neoplasm/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13 and 14</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Paget nipple disease/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget$ and (breast$ or mammary or nipple$)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17 or 18 or 19</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 or 20</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp aromatase inhibitor/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromatase inhibitor$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">anastrazole.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">arimidex.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letrozole.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">femara.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exemestane.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromasin.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">tamoxifen/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Nolvadex or tamoxifen$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/22-31</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 32</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">time factor/</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(duration$ or timing).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(sequenc$ or sequential).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">extended.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(continu$ or stop$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((optimal or different) adj (regimen$ or treatment or therapy or course)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(length adj2 (regimen$ or treatment or therapy or course)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/34-40</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33 and 41</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(“MA.17” or MA17 or ATTOM or ATLAS).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 43</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42 or 44</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 45 to yr=“1996 -Current”</td></tr><tr><td headers="hd_h_chd.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_chd.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Limit 46 to RCTs and SRs, and general exclusions filter applied</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab3"><div id="chd.appb.tab3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms, Ductal, Lobular, and Medullary] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Intraductal, Noninfiltrating] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Lobular] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Medullary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1 or #2 or #3 or #4 or #5</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 or #8</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next milk):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next tender*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10 or #11</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9 not #12</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13 and #14</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#18</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Paget’s Disease, Mammary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#19</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget* and (breast* or mammary or nipple*)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#20</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15 or #16 or #17 or #18 or #19</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6 or #20</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Aromatase Inhibitors] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#23</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromatase inhibitor*:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#24</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(anastrazole or arimidex or letrozole or femara or exemestane or aromasin):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#25</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Tamoxifen] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#26</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Nolvadex or tamoxifen*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#27</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22 or #23 or #24 or #25 or #26</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#28</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21 and #27</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#29</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Time Factors] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#30</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(duration* or timing):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(sequenc* or sequential):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">extended:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#33</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(continu* or stop*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#34</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((optimal or different) next (regimen* or treatment or therapy or course)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#35</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(length near/2 (regimen* or treatment or therapy or course)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#36</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#29 or #30 or #31 or #32 or #33 or #34 or #35</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#28 and #36</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#38</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(MA.17 or MA17 or ATTOM or ATLAS):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#39</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21 and #38</td></tr><tr><td headers="hd_h_chd.appb.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#40</td><td headers="hd_h_chd.appb.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37 or #39 Publication Year from 1996 to 2017</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab4"><div id="chd.appb.tab4" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab4_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast Neoplasms/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Neoplasms, Ductal, Lobular, and Medullary”/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Intraductal, Noninfiltrating/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Lobular/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Medullary/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 or 2 or 3 or 4 or 5</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 or 8</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj milk).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj tender$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 or 11</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 not 12</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Neoplasms/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13 and 14</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Paget’s Disease, Mammary/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget$ and (breast$ or mammary or nipple$)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17 or 18 or 19</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 or 20</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Ovariectomy/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovariectom$ or oophorectom$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(removal adj3 ovar$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((radiation or irradiation or radiotherap$) adj3 ovar$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Ovary/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Radiation/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovar$ adj3 (suppress$ or ablat$)).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26 and 27</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22 or 23 or 24 or 25 or 28 or 29</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 30</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Luteinizing Hormone/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">lutein$ hormon$ releas$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(LHRH$ or LH-RH$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Gonadotropin-Releasing Hormone/</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">gonadotrop$ releas$ hormon$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(GnRH$ or GnRHA$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(goserelin$ or zolade$ or novgos or buserelin$ or suprefact or suprecur or leuprolid$ or leuprorelin$ or lupron or nafarelin$ or synarel or triptorelin$ or decapeptyl or gonapeptyl).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(hormon$ adj3 (suppress$ or ablat$)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32 or 33 or 34 or 35 or 36 or 37 or 38 or 39</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 40</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31 or 41</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 42 to yr=“1992 -Current”</td></tr><tr><td headers="hd_h_chd.appb.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_chd.appb.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Limit 43 to RCTs and SRs, and general exclusions filter applied</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab5"><div id="chd.appb.tab5" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab5_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast cancer/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp medullary carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp intraductal carcinoma/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast tumor/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 or 2 or 3 or 4 or 5</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 or 8</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj milk).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj tender$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 or 11</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 not 12</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp neoplasm/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13 and 14</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Paget nipple disease/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget$ and (breast$ or mammary or nipple$)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 or 16 or 17 or 18 or 19</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 or 20</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp ovariectomy/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovariectom$ or oophorectom$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(removal adj3 ovar$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((radiation or irradiation or radiotherap$) adj3 ovar$).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp ovary/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp radiation/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovar$ adj3 (suppress$ or ablat$)).ti,ab.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26 and 27</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22 or 23 or 24 or 25 or 28 or 29</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 30</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp gonadorelin/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">lutein$ hormon$ releas$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(LHRH$ or LH-RH$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp growth hormone releasing factor/</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">gonadotrop$ releas$ hormon$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(GnRH$ or GnRHA$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(goserelin$ or zolade$ or novgos or buserelin$ or suprefact or suprecur or leuprolid$ or leuprorelin$ or lupron or nafarelin$ or synarel or triptorelin$ or decapeptyl or gonapeptyl).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(hormon$ adj3 (suppress$ or ablat$)).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32 or 33 or 34 or 35 or 36 or 37 or 38 or 39</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 and 40</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31 or 41</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 42 to yr=“1992 -Current”</td></tr><tr><td headers="hd_h_chd.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_chd.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Limit 43 to RCTs and SRs, and general exclusions filter applied</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab6"><div id="chd.appb.tab6" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab6_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms, Ductal, Lobular, and Medullary] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Intraductal, Noninfiltrating] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Lobular] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Medullary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1 or #2 or #3 or #4 or #5</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 or #8</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next milk):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next tender*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10 or #11</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9 not #12</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13 and #14</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#18</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Paget’s Disease, Mammary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#19</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget* and (breast* or mammary or nipple*)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#20</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15 or #16 or #17 or #18 or #19</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6 or #20</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Ovariectomy] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#23</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovariectom* or oophorectom*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#24</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(removal near/3 ovar*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#25</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((radiation or irradiation or radiotherap*) near/3 ovar*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#26</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Ovary] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#27</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Radiation] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#28</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ovar* near/3 (suppress* or ablat*)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#29</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#26 and #27</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#30</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22 or #23 or #24 or #25 or #28 or #29</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21 and #30</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Luteinizing Hormone] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#33</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">lutein* hormon* releas*:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#34</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(LHRH* or LH-RH*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#35</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Gonadotropin-Releasing Hormone] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#36</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">gonadotrop* releas* hormon*:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(GnRH* or GnRHA*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#38</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(goserelin* or zolade* or novgos or buserelin* or suprefact or suprecur or leuprolid* or leuprorelin* or lupron or nafarelin* or synarel or triptorelin* or decapeptyl or gonapeptyl):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#39</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(hormon* near/3 (suppress* or ablat*)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#40</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32 or #33 or #34 or #35 or #36 or #37 or #38 or #39</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#41</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21 and #40</td></tr><tr><td headers="hd_h_chd.appb.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#42</td><td headers="hd_h_chd.appb.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31 or #41 Publication Year from 1992 to 2016</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab7"><div id="chd.appb.tab7" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab7_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast cancer/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast carcinoma/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp medullary carcinoma/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp intraductal carcinoma/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast tumor/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast Neoplasms/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Neoplasms, Ductal, Lobular, and Medullary”/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Intraductal, Noninfiltrating/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Lobular/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carcinoma, Medullary/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp breast/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Breast/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast.tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12 or 13 or 14</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj milk).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast adj tender$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16 or 17</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15 not 18</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp neoplasm/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Neoplasms/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20 or 21</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19 and 22</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw. use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).tw. use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp. use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar$ adj5 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular)).mp. use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Paget nipple disease/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Paget’s Disease, Mammary/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget$ and (breast$ or mammary or nipple$)).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23 or 24 or 25 or 26 or 27 or 28 or 29 or 30</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11 or 31</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tamoxifen/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">tamoxifen/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Nolvadex$ or tamoxifen$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Aromatase Inhibitors/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp aromatase inhibitor/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromatase inhibitor$.mp.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(anastrazol$ or arimidex$ or letrozol$ or femara$ or exemestan$ or aromasin$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Selective Estrogen Receptor Modulators/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Raloxifene Hydrochloride/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp selective estrogen receptor modulator/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">raloxifene/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(raloxifen$ or evista$).mp.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32 and 45</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Primary Prevention/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Chemoprevention/ use prmz</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp primary prevention/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp chemoprophylaxis/ use oemezd</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(chemoprevent$ or chemoprophylax$).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(prevent$ adj3 (breast$ adj2 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular))).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(prevent$ adj3 (mammar$ adj2 (neoplasm$ or cancer$ or tumo?r$ or carcinoma$ or adenocarcinoma$ or sarcoma$ or leiomyosarcoma$ or dcis or duct$ or infiltrat$ or intraduct$ or lobul$ or medullary or tubular))).tw.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47 or 48 or 49 or 50 or 51 or 52 or 53</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46 and 54</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">remove duplicates from 55</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">prevent$.m_titl.</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46 and 57</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56 or 58</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">remove duplicates from 59</td></tr><tr><td headers="hd_h_chd.appb.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61</td><td headers="hd_h_chd.appb.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Limit 60 to RCTs and SRs, and general exclusions filter applied</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchdappbtab8"><div id="chd.appb.tab8" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appb.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appb.tab8_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#</th><th id="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Searches</th></tr></thead><tbody><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms, Ductal, Lobular, and Medullary] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Intraductal, Noninfiltrating] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Lobular] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carcinoma, Medullary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1 or #2 or #3 or #4 or #5</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Breast] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">breast:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 or #8</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next milk):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast next tender*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10 or #11</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9 not #12</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13 and #14</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(breast* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(mammar* near/5 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#18</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Paget’s Disease, Mammary] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#19</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(paget* and (breast* or mammary or nipple*)):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#20</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15 or #16 or #17 or #18 or #19</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6 or #20</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Aromatase Inhibitors] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#23</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">aromatase inhibitor*:ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#24</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(anastrazol* or arimidex* or letrozol* or femara* or exemestan* or aromasin*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#25</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Tamoxifen] this term only</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#26</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Nolvadex* or tamoxifen*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#27</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Selective Estrogen Receptor Modulators] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#28</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Raloxifene Hydrochloride] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#29</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(raloxifen* or evista*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#30</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22 or #23 or #24 or #25 or #26 or #27 or #28 or #29</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21 and #30</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Primary Prevention] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#33</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Chemoprevention] explode all trees</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#34</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(chemoprevent* or chemoprophylax*):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#35</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(prevent* near/3 (breast* near/2 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular))):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#36</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(prevent* near/3 (mammar* near/2 (neoplasm* or cancer* or tumo?r* or carcinoma* or adenocarcinoma* or sarcoma* or leiomyosarcoma* or dcis or duct* or infiltrat* or intraduct* or lobul* or medullary or tubular))):ti,ab,kw (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">prevent*:ti (Word variations have been searched)</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#38</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32 or #33 or #34 or #35 or #36 or #37</td></tr><tr><td headers="hd_h_chd.appb.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#39</td><td headers="hd_h_chd.appb.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31 and #38</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobchdappcfig1"><div id="chd.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Flow%20diagram%20of%20clinical%20article%20selection%20for%20duration%20of%20endocrine%20therapy.&p=BOOKS&id=576823_chdappcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappcf1.jpg" alt="Figure 1. Flow diagram of clinical article selection for duration of endocrine therapy." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Flow diagram of clinical article selection for duration of endocrine therapy</span></h3></div></article><article data-type="fig" id="figobchdappcfig2"><div id="chd.appc.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Flow%20diagram%20of%20clinical%20article%20selection%20for%20ovarian%20suppression%20review.&p=BOOKS&id=576823_chdappcf2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappcf2.jpg" alt="Figure 2. Flow diagram of clinical article selection for ovarian suppression review." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Flow diagram of clinical article selection for ovarian suppression review</span></h3></div></article><article data-type="fig" id="figobchdappcfig3"><div id="chd.appc.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20Flow%20diagram%20of%20clinical%20article%20selection%20for%20chemoprevention%20in%20DCIS.&p=BOOKS&id=576823_chdappcf3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappcf3.jpg" alt="Figure 3. Flow diagram of clinical article selection for chemoprevention in DCIS." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">Flow diagram of clinical article selection for chemoprevention in DCIS</span></h3></div></article><article data-type="fig" id="figobchdappefig4"><div id="chd.appe.fig4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20Disease%20free%20survival%20at%202.5%20to%2015%20year%20follow-up.&p=BOOKS&id=576823_chdappef4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef4.jpg" alt="Figure 4. Disease free survival at 2.5 to 15 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">Disease free survival at 2.5 to 15 year follow-up</span></h3><div class="caption"><p>Note. Number of events in each arm not reported for Scottish Adjuvant Tamoxifen Trial</p></div></div></article><article data-type="fig" id="figobchdappefig5"><div id="chd.appe.fig5" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%205.%20Disease%20free%20survival%20at%202.5%20to%2015%20year%20follow-up%3A%20tamoxifen%20and%20aromatase%20inhibitor%20subgroups.&p=BOOKS&id=576823_chdappef5.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef5.jpg" alt="Figure 5. Disease free survival at 2.5 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 5</span><span class="title">Disease free survival at 2.5 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups</span></h3><div class="caption"><p>Note. Number of events in each arm not reported for Scottish Adjuvant Tamoxifen Trial</p></div></div></article><article data-type="fig" id="figobchdappefig6"><div id="chd.appe.fig6" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%206.%20Overall%20survival%20at%204%20to%2015%20year%20follow-up.&p=BOOKS&id=576823_chdappef6.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef6.jpg" alt="Figure 6. Overall survival at 4 to 15 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 6</span><span class="title">Overall survival at 4 to 15 year follow-up</span></h3><div class="caption"><p>Note. Number of events in each arm not reported for Scottish Adjuvant Tamoxifen Trial</p></div></div></article><article data-type="fig" id="figobchdappefig7"><div id="chd.appe.fig7" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20Overall%20survival%20at%204%20to%2015%20year%20follow-up%3A%20tamoxifen%20and%20aromatase%20inhibitor%20subgroups.&p=BOOKS&id=576823_chdappef7.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef7.jpg" alt="Figure 7. Overall survival at 4 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">Overall survival at 4 to 15 year follow-up: tamoxifen and aromatase inhibitor subgroups</span></h3><div class="caption"><p>Note. Number of events in each arm not reported for Scottish Adjuvant Tamoxifen Trial</p></div></div></article><article data-type="fig" id="figobchdappefig8"><div id="chd.appe.fig8" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%208.%20Compliance%3A%20did%20not%20comply%20with%20assigned%20treatment.&p=BOOKS&id=576823_chdappef8.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef8.jpg" alt="Figure 8. Compliance: did not comply with assigned treatment." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 8</span><span class="title">Compliance: did not comply with assigned treatment</span></h3></div></article><article data-type="fig" id="figobchdappefig9"><div id="chd.appe.fig9" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%209.%20Treatment-related%20morbidity%3A%20hot%20flushes%20at%202%20month%20to%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef9.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef9.jpg" alt="Figure 9. Treatment-related morbidity: hot flushes at 2 month to 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 9</span><span class="title">Treatment-related morbidity: hot flushes at 2 month to 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig10"><div id="chd.appe.fig10" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2010.%20Treatment-related%20morbidity%3A%20secondary%20cancer%20at%205.6%20to%207.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef10.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef10.jpg" alt="Figure 10. Treatment-related morbidity: secondary cancer at 5.6 to 7.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 10</span><span class="title">Treatment-related morbidity: secondary cancer at 5.6 to 7.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig11"><div id="chd.appe.fig11" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2011.%20Treatment-related%20morbidity%3A%20bone%20fractures%20at%202%20month%20to%207.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef11.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef11.jpg" alt="Figure 11. Treatment-related morbidity: bone fractures at 2 month to 7.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 11</span><span class="title">Treatment-related morbidity: bone fractures at 2 month to 7.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig12"><div id="chd.appe.fig12" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2012.%20Treatment-related%20morbidity%3A%20arthralgia%20at%202%20month%20to%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef12.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef12.jpg" alt="Figure 12. Treatment-related morbidity: arthralgia at 2 month to 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 12</span><span class="title">Treatment-related morbidity: arthralgia at 2 month to 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig13"><div id="chd.appe.fig13" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2013.%20Treatment-related%20morbidity%3A%20cardiac%20disease%2Fevent%20at%202%20month%20to%207.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef13.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef13.jpg" alt="Figure 13. Treatment-related morbidity: cardiac disease/event at 2 month to 7.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 13</span><span class="title">Treatment-related morbidity: cardiac disease/event at 2 month to 7.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig14"><div id="chd.appe.fig14" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2014.%20Treatment-related%20morbidity%3A%20hypertension%20at%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef14.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef14.jpg" alt="Figure 14. Treatment-related morbidity: hypertension at 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 14</span><span class="title">Treatment-related morbidity: hypertension at 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig15"><div id="chd.appe.fig15" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2015.%20Treatment-related%20morbidity%3A%20osteoporosis%20at%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef15.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef15.jpg" alt="Figure 15. Treatment-related morbidity: osteoporosis at 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 15</span><span class="title">Treatment-related morbidity: osteoporosis at 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig16"><div id="chd.appe.fig16" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2016.%20Treatment-related%20morbidity%3A%20myalgia%20at%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef16.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef16.jpg" alt="Figure 16. Treatment-related morbidity: myalgia at 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 16</span><span class="title">Treatment-related morbidity: myalgia at 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig17"><div id="chd.appe.fig17" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2017.%20Treatment-related%20morbidity%3A%20any%20grade%203%2B%20toxicity%20at%202.5%20to%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef17.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef17.jpg" alt="Figure 17. Treatment-related morbidity: any grade 3+ toxicity at 2.5 to 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 17</span><span class="title">Treatment-related morbidity: any grade 3+ toxicity at 2.5 to 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig18"><div id="chd.appe.fig18" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2018.%20Treatment-related%20morbidity%3A%20vaginal%20dryness%20at%202%20month%20to%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef18.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef18.jpg" alt="Figure 18. Treatment-related morbidity: vaginal dryness at 2 month to 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 18</span><span class="title">Treatment-related morbidity: vaginal dryness at 2 month to 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig19"><div id="chd.appe.fig19" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2019.%20Treatment-related%20morbidity%3A%20vaginal%20bleeding%20at%202%20month%20to%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef19.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef19.jpg" alt="Figure 19. Treatment-related morbidity: vaginal bleeding at 2 month to 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 19</span><span class="title">Treatment-related morbidity: vaginal bleeding at 2 month to 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig20"><div id="chd.appe.fig20" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2020.%20Treatment-related%20morbidity%3A%20vaginal%20discharge%20at%202%20month%20to%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef20.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef20.jpg" alt="Figure 20. Treatment-related morbidity: vaginal discharge at 2 month to 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 20</span><span class="title">Treatment-related morbidity: vaginal discharge at 2 month to 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig21"><div id="chd.appe.fig21" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2021.%20Treatment-related%20morbidity%3A%20stroke%20at%207.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef21.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef21.jpg" alt="Figure 21. Treatment-related morbidity: stroke at 7.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 21</span><span class="title">Treatment-related morbidity: stroke at 7.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig22"><div id="chd.appe.fig22" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2022.%20Treatment-related%20morbidity%3A%20irregular%20menstruation%20at%204%20year%20follow-up.&p=BOOKS&id=576823_chdappef22.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef22.jpg" alt="Figure 22. Treatment-related morbidity: irregular menstruation at 4 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 22</span><span class="title">Treatment-related morbidity: irregular menstruation at 4 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig23"><div id="chd.appe.fig23" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2023.%20Treatment-related%20morbidity%3A%20phlebitis%2Fthromboembolic%20events%20at%202%20month%20to%207.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef23.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef23.jpg" alt="Figure 23. Treatment-related morbidity: phlebitis/thromboembolic events at 2 month to 7.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 23</span><span class="title">Treatment-related morbidity: phlebitis/thromboembolic events at 2 month to 7.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig24"><div id="chd.appe.fig24" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2024.%20HRQoL%3A%20change%20in%20SF-36%20scores%20from%20baseline%20(2%20year%20follow-up).&p=BOOKS&id=576823_chdappef24.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef24.jpg" alt="Figure 24. HRQoL: change in SF-36 scores from baseline (2 year follow-up)." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 24</span><span class="title">HRQoL: change in SF-36 scores from baseline (2 year follow-up)</span></h3><div class="caption"><p>Better indicated by higher values</p></div></div></article><article data-type="fig" id="figobchdappefig25"><div id="chd.appe.fig25" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2025.%20HRQoL%3A%20change%20in%20MENQOL%20scores%20from%20baseline%20(2%20year%20follow-up).&p=BOOKS&id=576823_chdappef25.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef25.jpg" alt="Figure 25. HRQoL: change in MENQOL scores from baseline (2 year follow-up)." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 25</span><span class="title">HRQoL: change in MENQOL scores from baseline (2 year follow-up)</span></h3><div class="caption"><p>Better indicated by lower values</p></div></div></article><article data-type="fig" id="figobchdappefig26"><div id="chd.appe.fig26" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2026.%20Overall%20survival%20at%205%20to%209.9%20year%20follow-up.&p=BOOKS&id=576823_chdappef26.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef26.jpg" alt="Figure 26. Overall survival at 5 to 9.9 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 26</span><span class="title">Overall survival at 5 to 9.9 year follow-up</span></h3><div class="caption"><p>Note. Number of events in each arm not reported for ABC trial</p></div></div></article><article data-type="fig" id="figobchdappefig27"><div id="chd.appe.fig27" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2027.%20Disease-free%20survival%20at%205%20to%209.9%20year%20follow-up.&p=BOOKS&id=576823_chdappef27.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef27.jpg" alt="Figure 27. Disease-free survival at 5 to 9.9 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 27</span><span class="title">Disease-free survival at 5 to 9.9 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig28"><div id="chd.appe.fig28" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2028.%20Treatment-related%20morbidity%3A%20vasodilation.&p=BOOKS&id=576823_chdappef28.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef28.jpg" alt="Figure 28. Treatment-related morbidity: vasodilation." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 28</span><span class="title">Treatment-related morbidity: vasodilation</span></h3></div></article><article data-type="fig" id="figobchdappefig29"><div id="chd.appe.fig29" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2029.%20Treatment-related%20morbidity%3A%20weight%20gain.&p=BOOKS&id=576823_chdappef29.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef29.jpg" alt="Figure 29. Treatment-related morbidity: weight gain." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 29</span><span class="title">Treatment-related morbidity: weight gain</span></h3></div></article><article data-type="fig" id="figobchdappefig30"><div id="chd.appe.fig30" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2030.%20Treatment-related%20morbidity%3A%20arthralgia.&p=BOOKS&id=576823_chdappef30.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef30.jpg" alt="Figure 30. Treatment-related morbidity: arthralgia." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 30</span><span class="title">Treatment-related morbidity: arthralgia</span></h3></div></article><article data-type="fig" id="figobchdappefig31"><div id="chd.appe.fig31" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2031.%20Treatment-related%20morbidity%3A%20anxiety%2Fdepression%2Firritability.&p=BOOKS&id=576823_chdappef31.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef31.jpg" alt="Figure 31. Treatment-related morbidity: anxiety/depression/irritability." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 31</span><span class="title">Treatment-related morbidity: anxiety/depression/irritability</span></h3></div></article><article data-type="fig" id="figobchdappefig32"><div id="chd.appe.fig32" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2032.%20Treatment-related%20morbidity%3A%20sweating.&p=BOOKS&id=576823_chdappef32.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef32.jpg" alt="Figure 32. Treatment-related morbidity: sweating." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 32</span><span class="title">Treatment-related morbidity: sweating</span></h3></div></article><article data-type="fig" id="figobchdappefig33"><div id="chd.appe.fig33" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2033.%20Treatment-related%20morbidity%3A%20hot%20flushes%20(grade%203%2B)%20at%203%20to%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef33.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef33.jpg" alt="Figure 33. Treatment-related morbidity: hot flushes (grade 3+) at 3 to 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 33</span><span class="title">Treatment-related morbidity: hot flushes (grade 3+) at 3 to 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig34"><div id="chd.appe.fig34" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2034.%20Treatment-related%20morbidity%3A%20hypertension%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef34.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef34.jpg" alt="Figure 34. Treatment-related morbidity: hypertension (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 34</span><span class="title">Treatment-related morbidity: hypertension (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig35"><div id="chd.appe.fig35" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2035.%20Treatment-related%20morbidity%3A%20cardiac%20ischemia%20or%20infarction%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef35.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef35.jpg" alt="Figure 35. Treatment-related morbidity: cardiac ischemia or infarction (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 35</span><span class="title">Treatment-related morbidity: cardiac ischemia or infarction (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig36"><div id="chd.appe.fig36" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2036.%20Treatment-related%20morbidity%3A%20thrombosis%20or%20embolism%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef36.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef36.jpg" alt="Figure 36. Treatment-related morbidity: thrombosis or embolism (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 36</span><span class="title">Treatment-related morbidity: thrombosis or embolism (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig37"><div id="chd.appe.fig37" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2037.%20Treatment-related%20morbidity%3A%20musculoskeletal%20symptoms%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef37.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef37.jpg" alt="Figure 37. Treatment-related morbidity: musculoskeletal symptoms (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 37</span><span class="title">Treatment-related morbidity: musculoskeletal symptoms (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig38"><div id="chd.appe.fig38" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2038.%20Treatment-related%20morbidity%3A%20osteoporosis%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef38.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef38.jpg" alt="Figure 38. Treatment-related morbidity: osteoporosis (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 38</span><span class="title">Treatment-related morbidity: osteoporosis (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig39"><div id="chd.appe.fig39" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2039.%20Treatment-related%20morbidity%3A%20fractures%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef39.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef39.jpg" alt="Figure 39. Treatment-related morbidity: fractures (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 39</span><span class="title">Treatment-related morbidity: fractures (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig40"><div id="chd.appe.fig40" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2040.%20Treatment-related%20morbidity%3A%20vaginal%20dryness%20at%203%20to%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef40.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef40.jpg" alt="Figure 40. Treatment-related morbidity: vaginal dryness at 3 to 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 40</span><span class="title">Treatment-related morbidity: vaginal dryness at 3 to 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig41"><div id="chd.appe.fig41" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2041.%20Treatment-related%20morbidity%3A%20changes%20in%20libido%20at%203%20to%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef41.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef41.jpg" alt="Figure 41. Treatment-related morbidity: changes in libido at 3 to 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 41</span><span class="title">Treatment-related morbidity: changes in libido at 3 to 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig42"><div id="chd.appe.fig42" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2042.%20Treatment-related%20morbidity%3A%20CNS%20cerebrovascular%20ischemia%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef42.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef42.jpg" alt="Figure 42. Treatment-related morbidity: CNS cerebrovascular ischemia (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 42</span><span class="title">Treatment-related morbidity: CNS cerebrovascular ischemia (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig43"><div id="chd.appe.fig43" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2043.%20Treatment-related%20morbidity%3A%20CNS%20haemorrhage%20(grade%203%2B)%20at%205.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef43.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef43.jpg" alt="Figure 43. Treatment-related morbidity: CNS haemorrhage (grade 3+) at 5.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 43</span><span class="title">Treatment-related morbidity: CNS haemorrhage (grade 3+) at 5.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig44"><div id="chd.appe.fig44" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2044.%20Treatment-related%20morbidity%3A%20vasomotor%20symptoms%20measured%20by%20Physical%20Symptoms%20and%20Problem%20List%20at%203%20year%20follow-up.&p=BOOKS&id=576823_chdappef44.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef44.jpg" alt="Figure 44. Treatment-related morbidity: vasomotor symptoms measured by Physical Symptoms and Problem List at 3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 44</span><span class="title">Treatment-related morbidity: vasomotor symptoms measured by Physical Symptoms and Problem List at 3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig45"><div id="chd.appe.fig45" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2045.%20Treatment-related%20morbidity%3A%20vaginal%20dryness%20measured%20by%20Physical%20Symptoms%20and%20Problem%20List%20at%203%20year%20follow-up.&p=BOOKS&id=576823_chdappef45.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef45.jpg" alt="Figure 45. Treatment-related morbidity: vaginal dryness measured by Physical Symptoms and Problem List at 3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 45</span><span class="title">Treatment-related morbidity: vaginal dryness measured by Physical Symptoms and Problem List at 3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig46"><div id="chd.appe.fig46" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2046.%20Treatment-related%20morbidity%3A%20changes%20in%20total%20body%20bone%20density%20(g%2Fcm2)%20at%202%20year%20follow-up.&p=BOOKS&id=576823_chdappef46.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef46.jpg" alt="Figure 46. Treatment-related morbidity: changes in total body bone density (g/cm2) at 2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 46</span><span class="title">Treatment-related morbidity: changes in total body bone density (g/cm<sup>2</sup>) at 2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig47"><div id="chd.appe.fig47" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2047.%20Compliance%3A%20treatment%20completed.&p=BOOKS&id=576823_chdappef47.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef47.jpg" alt="Figure 47. Compliance: treatment completed." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 47</span><span class="title">Compliance: treatment completed</span></h3></div></article><article data-type="fig" id="figobchdappefig48"><div id="chd.appe.fig48" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2048.%20HRQoL%3A%20FACT-G.&p=BOOKS&id=576823_chdappef48.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef48.jpg" alt="Figure 48. HRQoL: FACT-G." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 48</span><span class="title">HRQoL: FACT-G</span></h3></div></article><article data-type="fig" id="figobchdappefig49"><div id="chd.appe.fig49" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2049.%20HRQoL%3A%20FACT-B.&p=BOOKS&id=576823_chdappef49.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef49.jpg" alt="Figure 49. HRQoL: FACT-B." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 49</span><span class="title">HRQoL: FACT-B</span></h3></div></article><article data-type="fig" id="figobchdappefig50"><div id="chd.appe.fig50" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2050.%20Disease-free%20survival%20at%2010%20year%20follow-up.&p=BOOKS&id=576823_chdappef50.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef50.jpg" alt="Figure 50. Disease-free survival at 10 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 50</span><span class="title">Disease-free survival at 10 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig51"><div id="chd.appe.fig51" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2051.%20Local%20recurrence%20survival%20at%2010%20to%2013.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef51.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef51.jpg" alt="Figure 51. Local recurrence survival at 10 to 13.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 51</span><span class="title">Local recurrence survival at 10 to 13.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig52"><div id="chd.appe.fig52" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2052.%20Overall%20survival%20at%2013.6%20year%20follow-up.&p=BOOKS&id=576823_chdappef52.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef52.jpg" alt="Figure 52. Overall survival at 13.6 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 52</span><span class="title">Overall survival at 13.6 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig53"><div id="chd.appe.fig53" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2053.%20Treatment-related%20morbidity%3A%20vaginal%20dryness%2Fdischarge%20at%203.3%20to%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef53.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef53.jpg" alt="Figure 53. Treatment-related morbidity: vaginal dryness/discharge at 3.3 to 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 53</span><span class="title">Treatment-related morbidity: vaginal dryness/discharge at 3.3 to 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig54"><div id="chd.appe.fig54" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2054.%20Treatment-related%20morbidity%3A%20grade%203%2B%20toxicities%20at%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef54.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef54.jpg" alt="Figure 54. Treatment-related morbidity: grade 3+ toxicities at 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 54</span><span class="title">Treatment-related morbidity: grade 3+ toxicities at 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig55"><div id="chd.appe.fig55" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2055.%20Treatment-related%20morbidity%3A%20phlebitis%2Fthromboembolism%20at%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef55.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef55.jpg" alt="Figure 55. Treatment-related morbidity: phlebitis/thromboembolism at 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 55</span><span class="title">Treatment-related morbidity: phlebitis/thromboembolism at 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig56"><div id="chd.appe.fig56" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2056.%20Treatment-related%20morbidity%3A%20mood%20changes%20at%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef56.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef56.jpg" alt="Figure 56. Treatment-related morbidity: mood changes at 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 56</span><span class="title">Treatment-related morbidity: mood changes at 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig57"><div id="chd.appe.fig57" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2057.%20Treatment-related%20morbidity%3A%20menstrual%20disorders%20at%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef57.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef57.jpg" alt="Figure 57. Treatment-related morbidity: menstrual disorders at 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 57</span><span class="title">Treatment-related morbidity: menstrual disorders at 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig58"><div id="chd.appe.fig58" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2058.%20Treatment-related%20morbidity%3A%20hot%20flashes%20at%203.3%20to%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef58.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef58.jpg" alt="Figure 58. Treatment-related morbidity: hot flashes at 3.3 to 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 58</span><span class="title">Treatment-related morbidity: hot flashes at 3.3 to 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig59"><div id="chd.appe.fig59" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2059.%20Treatment-related%20morbidity%3A%20fluid%20retention%20at%206.2%20year%20follow-up.&p=BOOKS&id=576823_chdappef59.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef59.jpg" alt="Figure 59. Treatment-related morbidity: fluid retention at 6.2 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 59</span><span class="title">Treatment-related morbidity: fluid retention at 6.2 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig60"><div id="chd.appe.fig60" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2060.%20Treatment-related%20morbidity%3A%20ocular%2Fvisual%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef60.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef60.jpg" alt="Figure 60. Treatment-related morbidity: ocular/visual at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 60</span><span class="title">Treatment-related morbidity: ocular/visual at 3.3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig61"><div id="chd.appe.fig61" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2061.%20Treatment-related%20morbidity%3A%20dermatological%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef61.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef61.jpg" alt="Figure 61. Treatment-related morbidity: dermatological at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 61</span><span class="title">Treatment-related morbidity: dermatological at 3.3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig62"><div id="chd.appe.fig62" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2062.%20Treatment-related%20morbidity%3A%20dysuria%2Fincontinence%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef62.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef62.jpg" alt="Figure 62. Treatment-related morbidity: dysuria/incontinence at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 62</span><span class="title">Treatment-related morbidity: dysuria/incontinence at 3.3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig63"><div id="chd.appe.fig63" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2063.%20Treatment-related%20morbidity%3A%20vaginal%20bleeding%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef63.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef63.jpg" alt="Figure 63. Treatment-related morbidity: vaginal bleeding at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 63</span><span class="title">Treatment-related morbidity: vaginal bleeding at 3.3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig64"><div id="chd.appe.fig64" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2064.%20Treatment-related%20morbidity%3A%20endometrial%20polyps%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef64.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef64.jpg" alt="Figure 64. Treatment-related morbidity: endometrial polyps at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 64</span><span class="title">Treatment-related morbidity: endometrial polyps at 3.3 year follow-up</span></h3></div></article><article data-type="fig" id="figobchdappefig65"><div id="chd.appe.fig65" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2065.%20Treatment-related%20morbidity%3A%20sweats%2Fweight%20gain%20at%203.3%20year%20follow-up.&p=BOOKS&id=576823_chdappef65.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK576823/bin/chdappef65.jpg" alt="Figure 65. Treatment-related morbidity: sweats/weight gain at 3.3 year follow-up." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 65</span><span class="title">Treatment-related morbidity: sweats/weight gain at 3.3 year follow-up</span></h3></div></article><article data-type="table-wrap" id="figobchdappitab1"><div id="chd.appi.tab1" class="table"><h3><span class="label">Table 17</span><span class="title">Summary table showing the included health economic evidence for the optimal duration of adjuvant endocrine therapy for people with oestrogen-receptor positive breast cancer</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK576823/table/chd.appi.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd.appi.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_chd.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_chd.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Comparators</th><th id="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Costs</th><th id="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Effects</th><th id="hd_h_chd.appi.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Incr costs</th><th id="hd_h_chd.appi.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Incr effects</th><th id="hd_h_chd.appi.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">ICER</th><th id="hd_h_chd.appi.tab1_1_1_1_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Uncertainty</th><th id="hd_h_chd.appi.tab1_1_1_1_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Applicability and limitations</th></tr></thead><tbody><tr><td headers="hd_h_chd.appi.tab1_1_1_1_1" rowspan="9" colspan="1" style="text-align:left;vertical-align:top;">Erman 2014</td><td headers="hd_h_chd.appi.tab1_1_1_1_2" rowspan="8" colspan="1" style="text-align:left;vertical-align:top;">Post-menopausal women with early stage (stage I-III) HR+ breast cancer.</td><td headers="hd_h_chd.appi.tab1_1_1_1_3 hd_h_chd.appi.tab1_1_1_1_4 hd_h_chd.appi.tab1_1_1_1_5 hd_h_chd.appi.tab1_1_1_1_6 hd_h_chd.appi.tab1_1_1_1_7 hd_h_chd.appi.tab1_1_1_1_8" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">Comparison against standard tamoxifen</td><td headers="hd_h_chd.appi.tab1_1_1_1_9" rowspan="8" colspan="1" style="text-align:left;vertical-align:top;">
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<p>A series of one-way sensitivity analyses were conducted exploring changes in costs and clinical inputs.</p>
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<p>The result was found to be sensitive to changes in the cost of aromatase inhibitors and the probability of recurrence when taking aromatase inhibitors or tamoxifen.</p>
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<p>Probabilistic sensitivity analysis was conducted. At the conventional threshold of $50,000 (CAD) per QALY, the probability of being cost-effective was 70% for extended aromatase inhibitors, 30% for extended tamoxifen and 0.003% for standard tamoxifen.</p>
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</td><td headers="hd_h_chd.appi.tab1_1_1_1_10" rowspan="8" colspan="1" style="text-align:left;vertical-align:top;">
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<p>The study was deemed to be only partially applicable to the UK because it considered the perspective of the Canadian health care system.</p>
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<p>The study was generally thought to be of good quality but some potentially serious limitations were noted such as the absence of some potentially key parameters from sensitivity analysis (utility weights).</p>
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</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Standard tamoxifen</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$9,343.66 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.12 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6 hd_h_chd.appi.tab1_1_1_1_7 hd_h_chd.appi.tab1_1_1_1_8" colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">Reference</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Extended tamoxifen</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$8,623.06 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.38 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-$720.60 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.26 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dominant</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Extended aromatase inhibitors</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$9,432.73 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.62 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$89.07 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.50 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$178.14 (CAD)</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3 hd_h_chd.appi.tab1_1_1_1_4 hd_h_chd.appi.tab1_1_1_1_5 hd_h_chd.appi.tab1_1_1_1_6 hd_h_chd.appi.tab1_1_1_1_7 hd_h_chd.appi.tab1_1_1_1_8" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">Dominance rank</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Extended tamoxifen</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$8,623.06 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.38 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6 hd_h_chd.appi.tab1_1_1_1_7 hd_h_chd.appi.tab1_1_1_1_8" colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">Reference</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Standard tamoxifen</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$9,343.66 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.12 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$720.60 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-0.26 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dominated</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Extended aromatase inhibitors</td><td headers="hd_h_chd.appi.tab1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$9,432.73 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.62 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$809.66 (CAD)</td><td headers="hd_h_chd.appi.tab1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.24 QALYs</td><td headers="hd_h_chd.appi.tab1_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">$3,402.38 (CAD) per QALY</td></tr><tr><td headers="hd_h_chd.appi.tab1_1_1_1_2 hd_h_chd.appi.tab1_1_1_1_3 hd_h_chd.appi.tab1_1_1_1_4 hd_h_chd.appi.tab1_1_1_1_5 hd_h_chd.appi.tab1_1_1_1_6 hd_h_chd.appi.tab1_1_1_1_7 hd_h_chd.appi.tab1_1_1_1_8 hd_h_chd.appi.tab1_1_1_1_9 hd_h_chd.appi.tab1_1_1_1_10" colspan="9" rowspan="1" style="text-align:left;vertical-align:top;">
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<p><b>Comments:</b> Strategies compared using ‘dominance rank’ approach to determine optimal strategy overall. Strategies are first ranked in terms of cost (least costly to most costly). The second intervention in the list is then compared against the first strategy. Subsequent strategies are then compared against the previous strategy that was found to be cost-effective.</p>
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<p>Strategies compared against standard tamoxifen were not reported in study but have been estimated here as they were of most relevance to the review question.</p>
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