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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2023/09/21">
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<meta name="citation_author" content="Nancie Petrucelli">
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<meta name="citation_author" content="Mary B Daly">
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<meta name="citation_author" content="Tuya Pal">
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<meta name="citation_keywords" content="BRCA1- and BRCA2-Associated HBOC">
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<meta name="citation_keywords" content="BRCA1- and BRCA2-Associated HBOC">
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<meta name="citation_keywords" content="Breast cancer type 1 susceptibility protein">
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<meta name="citation_keywords" content="Breast cancer type 2 susceptibility protein">
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<meta name="citation_keywords" content="BRCA1">
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<meta name="citation_keywords" content="BRCA2">
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<meta name="DC.Title" content="BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Nancie Petrucelli">
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<meta name="DC.Contributor" content="Mary B Daly">
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<meta name="DC.Contributor" content="Tuya Pal">
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<meta name="description" content="BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The risk of developing an associated cancer varies depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.">
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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1247_"><span class="title" itemprop="name"><i>BRCA1-</i> and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>BRCA1</i>- and <i>BRCA2</i>-Associated HBOC</div><p class="contribs">Petrucelli N, Daly MB, Pal T.</p><p class="fm-aai"><a href="#_NBK1247_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 57 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="brca1.Summary" itemprop="description"><h2 id="_brca1_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>BRCA1-</i> and <i>BRCA2-</i>associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a <i>BRCA2</i> pathogenic variant. The risk of developing an associated cancer varies depending on whether HBOC is caused by a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant<i>.</i></p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC is established in a proband by identification of a heterozygous germline pathogenic variant in <i>BRCA1</i> or <i>BRCA2</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment of breast cancer per oncologist with consideration of bilateral mastectomy as a primary surgical treatment of breast cancer because of elevated rate of ipsilateral and contralateral breast cancer; PARP inhibitors may be considered in <i>BRCA1-</i> and <i>BRCA2</i>-related tumors. Melanoma treatment per dermatologist and oncologist.</p><p><i>Prevention of primary manifestations:</i> Prophylactic bilateral mastectomy, prophylactic oophorectomy, and chemoprevention (e.g., tamoxifen) have been used for breast cancer prevention, but have not been assessed by randomized trials in high-risk women. Prophylactic salpingectomy followed by delayed oophorectomy or salpingo-oophorectomy for ovarian cancer prevention.</p><p><i>Surveillance:</i> Breast cancer screening in women relies on a combination of monthly breast self-examination, annual or semiannual clinical breast examination, annual mammography, and breast MRI. Annual transvaginal ultrasound and serum CA-125 concentration beginning at age 35 years may be considered for ovarian cancer screening. However, this screening has not been effective in detecting early-stage ovarian cancer, either in high-risk or average-risk women. For men, breast cancer screening includes breast self-examination education and training and annual clinical breast examination beginning at age 35. Annual serum prostate-specific antigen and digital rectal exam screening should begin at age 45. Screening for melanoma should be individualized based on the family history. Screening of asymptomatic individuals for pancreatic cancer is not generally recommended.</p><p><i>Evaluation of relatives at risk:</i> Once a cancer-predisposing <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial pathogenic variant and thus need increased surveillance and specific treatments when a cancer is identified.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>BRCA1-</i> and <i>BRCA2-</i>associated HBOC is inherited in an autosomal dominant manner. The vast majority of individuals with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant inherited it from a parent. However, because the penetrance of breast, ovarian, and other cancers associated with pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> is less than 100%, not all individuals with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant have a parent affected with cancer. The offspring of an individual with a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant have a 50% chance of inheriting the pathogenic variant. Once a cancer-predisposing <i>BRCA1</i> or <i>BRCA2</i> germline variant has been identified in a family, prenatal and preimplantation genetic testing are possible.</p></div></div><div id="brca1.Diagnosis"><h2 id="_brca1_Diagnosis_">Diagnosis</h2><div id="brca1.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>BRCA1-</i> and <i>BRCA2</i>-associated hereditary breast and ovarian cancer (HBOC) <b>should be suspected</b> in individuals with a personal or family history (first-, second-, or third-degree relative in either lineage) of any of the following:</p><ul><li class="half_rhythm"><div>Breast cancer diagnosed at or before age 50 years</div></li><li class="half_rhythm"><div>Ovarian cancer</div></li><li class="half_rhythm"><div>Multiple (i.e., >1) primary breast cancers in either one or both breasts</div></li><li class="half_rhythm"><div>Male breast cancer</div></li><li class="half_rhythm"><div>Triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer</div></li><li class="half_rhythm"><div>The combination of pancreatic cancer and/or prostate cancer (metastatic or Gleason score ≥7) with breast cancer and/or ovarian cancer</div></li><li class="half_rhythm"><div>Breast cancer diagnosed at any age in an individual of Ashkenazi Jewish ancestry</div></li><li class="half_rhythm"><div>Two or more relatives with breast cancer, one diagnosed at or before age 50 years</div></li><li class="half_rhythm"><div>Three or more relatives with breast cancer at any age</div></li><li class="half_rhythm"><div>A family member with a known <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant</div></li></ul><p>Note: (1) "Breast cancer" includes both invasive cancer and ductal carcinoma in situ. (2) "Ovarian cancer" includes epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.</p><div id="brca1.Probability_Models_for_BRCA1_and_B"><h4>Probability Models for <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variants</h4><p>Several models have been developed to estimate the likelihood that an individual or family has a germline pathogenic variant in <i>BRCA1</i> or <i>BRCA2</i> [<a class="bibr" href="#brca1.REF.parmigiani.1998.145" rid="brca1.REF.parmigiani.1998.145">Parmigiani et al 1998</a>, <a class="bibr" href="#brca1.REF.frank.2002.1480" rid="brca1.REF.frank.2002.1480">Frank et al 2002</a>, <a class="bibr" href="#brca1.REF.antoniou.2004.1580" rid="brca1.REF.antoniou.2004.1580">Antoniou et al 2004</a>, <a class="bibr" href="#brca1.REF.evans.2004.474" rid="brca1.REF.evans.2004.474">Evans et al 2004</a>, <a class="bibr" href="#brca1.REF.tyrer.2004.1111" rid="brca1.REF.tyrer.2004.1111">Tyrer et al 2004</a>]. Even among experienced providers, the use of probability models has been shown to increase the ability to identify which individuals are more likely to have a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant [<a class="bibr" href="#brca1.REF.euhus.2002.844" rid="brca1.REF.euhus.2002.844">Euhus et al 2002</a>, <a class="bibr" href="#brca1.REF.de_la_hoya.2003.503" rid="brca1.REF.de_la_hoya.2003.503">de la Hoya et al 2003</a>]. For more information about probability models for <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants, click <a href="/books/NBK1247/bin/brca1-probability_models.pdf">here</a>.</p></div></div><div id="brca1.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC <b>is established</b> in a proband by identification of a heterozygous germline pathogenic (or likely pathogenic) variant in <i>BRCA1</i> or <i>BRCA2</i> on molecular genetic testing (see <a href="/books/NBK1247/table/brca1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobbrca1Tmoleculargenetictestingusedi">Table 1</a>).</p><p>Note: (1) Molecular testing is most likely to be informative in an individual with a <i>BRCA1-</i> or <i>BRCA2</i>-associated cancer (e.g., breast cancer at age <50 years, ovarian cancer; this individual is often referred to as the "best test candidate." Thus, molecular genetic testing ideally should be performed initially on the "best test candidate" as opposed to a family member who may have an unrelated cancer or who may not have a personal history of cancer. (2) If the best test candidate is not available, molecular testing may be performed on another individual, without a cancer history, with the understanding that failure to detect a pathogenic variant does not eliminate the possibility of a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant being present in the family. (3) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#brca1.REF.richards.2015.405" rid="brca1.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include likely pathogenic variants. (4) Identification of a heterozygous <i>BRCA1</i> or <i>BRCA2</i> variant of uncertain significance does not establish or rule out the diagnosis.</p><p>Molecular testing approaches can include a <b><i>BRCA1</i> and <i>BRCA2</i> gene panel</b> and use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b><i>BRCA1</i> and <i>BRCA2</i> gene panel<i>.</i></b> Sequence analysis of <i>BRCA1</i> and <i>BRCA2</i> is performed concurrently with deletion/duplication analysis.</div><div class="half_rhythm">Targeted analysis can be considered in individuals of Ashkenazi Jewish ancestry by starting with targeted testing for three <i>BRCA1</i> and <i>BRCA2</i> pathogenic founder variants: <i>BRCA1</i> c.68_69delAG (BIC: 185delAG) <i>BRCA1</i> c.5266dupC (BIC: 5382insC), and <i>BRCA2</i> c.5946delT (BIC: 6174delT), which together account for up to 99% of pathogenic variants identified in individuals of Ashkenazi Jewish ancestry. If no pathogenic variant is identified by targeted analysis, it may be appropriate to proceed with sequence analysis and deletion/duplication analysis of <i>BRCA1</i> and <i>BRCA2</i> or a multigene panel.</div><div class="half_rhythm">Note: In a family known to have a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant, relatives at risk may only need testing for the family-specific germline pathogenic variant, except in the following situations:</div><ul><li class="half_rhythm"><div>Individuals of Ashkenazi Jewish descent should consider testing for all three founder pathogenic variants because of the high population frequency of these variants as well as reports of the coexistence of more than one founder variant in some families. They may also consider multigene panel testing, depending on their personal and family history.</div></li><li class="half_rhythm"><div>Individuals with a familial <i>BRCA1</i> or <i>BRACA2</i> pathogenic variant on one side of the family and characteristics of HBOC or another inherited cancer syndrome on either the same side or the other side of the family may consider sequence analysis and deletion/duplication analysis of <i>BRCA1</i> and <i>BRCA2</i> or a multigene panel, which would detect the familial germline pathogenic variant (if present) and also address whether another germline pathogenic variant may be present.</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm">A <b>multigene panel</b> that includes <i>BRCA1</i>, <i>BRCA2</i>, and other genes of interest (see <a href="#brca1.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Tmoleculargenetictestingusedi"><a href="/books/NBK1247/table/brca1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobbrca1Tmoleculargenetictestingusedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.molecular_genetic_testing_used_i"><a href="/books/NBK1247/table/brca1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobbrca1Tmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>BRCA1-</i> and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer </p></div></div></div></div><div id="brca1.Clinical_Characteristics"><h2 id="_brca1_Clinical_Characteristics_">Clinical Characteristics</h2><div id="brca1.Clinical_Description"><h3>Clinical Description</h3><p><i>BRCA1-</i> and <i>BRCA2-</i>associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for male and female breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate, pancreatic, and melanoma, primarily in individuals with a <i>BRCA2</i> pathogenic variant. Estimates of malignancy risk vary considerably depending on the context in which they were derived. <a href="/books/NBK1247/table/brca1.T.risk_of_malignancy_in_individual/?report=objectonly" target="object" rid-ob="figobbrca1Triskofmalignancyinindividual">Table 2</a> is a summary of the risk for malignancy in an individual with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Triskofmalignancyinindividual"><a href="/books/NBK1247/table/brca1.T.risk_of_malignancy_in_individual/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobbrca1Triskofmalignancyinindividual"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.risk_of_malignancy_in_individual"><a href="/books/NBK1247/table/brca1.T.risk_of_malignancy_in_individual/?report=objectonly" target="object" rid-ob="figobbrca1Triskofmalignancyinindividual">Table 2. </a></h4><p class="float-caption no_bottom_margin">Risk of Malignancy in Individuals with a Germline <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variant </p></div></div><p><b>Breast cancer.</b> Compared to sporadic tumors, <i>BRCA1</i>-related tumors show an excess of medullary histopathology, are of higher histologic grade, are more likely to be estrogen receptor negative and progesterone receptor negative, and are less likely to demonstrate human epidermal growth factor receptor 2 overexpression; thus, <i>BRCA1</i>-related tumors fall within the category of "triple-negative" breast cancer [<a class="bibr" href="#brca1.REF.rakha.2008.2568" rid="brca1.REF.rakha.2008.2568">Rakha et al 2008</a>, <a class="bibr" href="#brca1.REF.lee.2011.4373" rid="brca1.REF.lee.2011.4373">Lee et al 2011</a>, <a class="bibr" href="#brca1.REF.mavaddat.2012.134" rid="brca1.REF.mavaddat.2012.134">Mavaddat et al 2012</a>] and overlap with basal-like breast cancers.</p><p>The histologic characteristics of <i>BRCA2</i>-related tumors have been inconsistent but appear to be more heterogeneous and are less well characterized than <i>BRCA1</i>-related tumors. They are generally estrogen and progesterone receptor positive; however, a large international series of 2,392 individuals with <i>BRCA2</i> germline pathogenic variants found that 16% had triple-negative tumors [<a class="bibr" href="#brca1.REF.mavaddat.2012.134" rid="brca1.REF.mavaddat.2012.134">Mavaddat et al 2012</a>].</p><p>The evidence that a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant is associated with poor survival in individuals with breast cancer has been inconsistent [<a class="bibr" href="#brca1.REF.verhoog.2000.119s" rid="brca1.REF.verhoog.2000.119s">Verhoog et al 2000</a>, <a class="bibr" href="#brca1.REF.bordeleau.2010.13" rid="brca1.REF.bordeleau.2010.13">Bordeleau et al 2010</a>, <a class="bibr" href="#brca1.REF.van_den_broek.2015.e0120189" rid="brca1.REF.van_den_broek.2015.e0120189">van den Broek et al 2015</a>, <a class="bibr" href="#brca1.REF.zhong.2015.211" rid="brca1.REF.zhong.2015.211">Zhong et al 2015</a>].</p><p><b>Contralateral breast cancer (CBC).</b> Several studies have reported higher rates of CBC [<a class="bibr" href="#brca1.REF.metcalfe.2011a.1384" rid="brca1.REF.metcalfe.2011a.1384">Metcalfe et al 2011a</a>, <a class="bibr" href="#brca1.REF.vichapat.2012.3478" rid="brca1.REF.vichapat.2012.3478">Vichapat et al 2012</a>, <a class="bibr" href="#brca1.REF.van_den_broek.2015.e0120189" rid="brca1.REF.van_den_broek.2015.e0120189">van den Broek et al 2015</a>] in women treated conservatively. Predictors of CBC include age at first breast cancer, family history of early-onset breast cancer, and the affected <i>BRCA</i> gene [<a class="bibr" href="#brca1.REF.graeser.2009.5887" rid="brca1.REF.graeser.2009.5887">Graeser et al 2009</a>, <a class="bibr" href="#brca1.REF.malone.2010.2404" rid="brca1.REF.malone.2010.2404">Malone et al 2010</a>, <a class="bibr" href="#brca1.REF.metcalfe.2011a.1384" rid="brca1.REF.metcalfe.2011a.1384">Metcalfe et al 2011a</a>, <a class="bibr" href="#brca1.REF.van_den_broek.2015.e0120189" rid="brca1.REF.van_den_broek.2015.e0120189">van den Broek et al 2015</a>]. The risk of CBC is greatest among women whose initial breast cancer occurs at a young age. Most studies show an excess of CBC among individuals with a <i>BRCA1</i> pathogenic variant when compared to individuals with a <i>BRCA2</i> pathogenic variant. The risk for CBC was decreased among women who had undergone prophylactic oophorectomy [<a class="bibr" href="#brca1.REF.metcalfe.2011a.1384" rid="brca1.REF.metcalfe.2011a.1384">Metcalfe et al 2011a</a>]; there was no clear association between the use of radiation therapy and an increased risk of CBC in individuals with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</p><p><b>Ipsilateral breast cancer.</b> Two case-control studies reported significantly higher rates of ipsilateral breast cancer in individuals with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant compared with sporadic controls [<a class="bibr" href="#brca1.REF.haffty.2002.1471" rid="brca1.REF.haffty.2002.1471">Haffty et al 2002</a>, <a class="bibr" href="#brca1.REF.seynaeve.2004.1150" rid="brca1.REF.seynaeve.2004.1150">Seynaeve et al 2004</a>], however, other studies have not found an increased risk for ipsilateral breast cancer in those with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant when compared with women who had sporadic breast cancer [<a class="bibr" href="#brca1.REF.robson.2004.r8" rid="brca1.REF.robson.2004.r8">Robson et al 2004</a>, <a class="bibr" href="#brca1.REF.graeser.2009.5887" rid="brca1.REF.graeser.2009.5887">Graeser et al 2009</a>] and also demonstrated a significant ipsilateral breast cancer risk reduction in individuals receiving radiation therapy compared with those who did not receive radiation therapy [<a class="bibr" href="#brca1.REF.metcalfe.2011b.287" rid="brca1.REF.metcalfe.2011b.287">Metcalfe et al 2011b</a>].</p><p><b>Ovarian cancer (including fallopian tube and primary peritoneal cancers).</b> An excess of serous adenocarcinomas as opposed to mucinous or borderline tumors have been observed in women with germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants [<a class="bibr" href="#brca1.REF.liu.2012.34" rid="brca1.REF.liu.2012.34">Liu et al 2012</a>, <a class="bibr" href="#brca1.REF.mclaughlin.2013.141" rid="brca1.REF.mclaughlin.2013.141">McLaughlin et al 2013</a>]. Serous adenocarcinomas are generally of higher grade and exhibit prominent intraepithelial lymphocytes, marked nuclear atypia, and abundant mitoses [<a class="bibr" href="#brca1.REF.fujiwara.2012.1170" rid="brca1.REF.fujiwara.2012.1170">Fujiwara et al 2012</a>]. Most high-grade serous cancers arise from the fallopian tubes rather than the ovaries [<a class="bibr" href="#brca1.REF.daly.2015.342" rid="brca1.REF.daly.2015.342">Daly et al 2015</a>].</p><p>Studies on ovarian cancer survival in women with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant have yielded conflicting results. A pooled analysis of 26 observational studies found a more favorable survival rate among individuals with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant compared to individuals without a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant. These results persisted when controlling for stage, grade, histology, and age at diagnosis [<a class="bibr" href="#brca1.REF.bolton.2012.382" rid="brca1.REF.bolton.2012.382">Bolton et al 2012</a>]. A large population-based case-control study found a higher response to platinum-based therapy, longer progression-free survival, and improved overall survival among individuals with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant [<a class="bibr" href="#brca1.REF.alsop.2012.2654" rid="brca1.REF.alsop.2012.2654">Alsop et al 2012</a>]. Similarly, individuals with platinum-sensitive epithelial ovarian tumors were more likely to have a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant than individuals with platinum-resistant tumors [<a class="bibr" href="#brca1.REF.dann.2012.677" rid="brca1.REF.dann.2012.677">Dann et al 2012</a>]. In a large series of unselected individuals with ovarian cancer, the short-term survival of individuals with ovarian cancer with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant was better than that of individuals without an identified <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant; however, the survival advantage was short lived and did not lead to a long-term survival benefit [<a class="bibr" href="#brca1.REF.mclaughlin.2013.141" rid="brca1.REF.mclaughlin.2013.141">McLaughlin et al 2013</a>].</p><p><b>Male breast cancer.</b> The majority of <i>BRCA1</i>- and <i>BRCA2</i>-associated male breast cancers, particularly those associated with <i>BRCA2</i> pathogenic variants, are high grade, hormone receptor positive, and associated with lymph node metastases. Despite having high-grade histology, males with <i>BRCA1</i>- or <i>BRCA2</i>-associated breast cancer have demonstrated a favorable five-year survival [<a class="bibr" href="#brca1.REF.ibrahim.2018.179" rid="brca1.REF.ibrahim.2018.179">Ibrahim et al 2018</a>].</p><p><b>Prostate cancer.</b>
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<i>BRCA2</i>-related prostate cancer is more likely to be associated with features of aggressive disease, including a higher tumor stage and/or higher grade at diagnosis, higher Gleason scores [<a class="bibr" href="#brca1.REF.gallagher.2010.2115" rid="brca1.REF.gallagher.2010.2115">Gallagher et al 2010</a>], and a higher prostate-specific antigen level at diagnosis [<a class="bibr" href="#brca1.REF.ibrahim.2018.179" rid="brca1.REF.ibrahim.2018.179">Ibrahim et al 2018</a>].</p><p><b>Pancreatic cancer.</b>
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<i>BRCA1</i> and <i>BRCA2</i> are among the most common of the known genetic causes of hereditary pancreatic ductal adenocarcinoma (PDAC) with a mean age at diagnosis of approximately 60.3 years (range 33-83 years) [<a class="bibr" href="#brca1.REF.golan.2014.1132" rid="brca1.REF.golan.2014.1132">Golan et al 2014</a>]. There is accumulating evidence of increased sensitivity to platinum-based therapy and poly ADP ribose polymerase (PARP) inhibitors in <i>BRCA1</i>- and <i>BRCA2</i>-associated PDAC [<a class="bibr" href="#brca1.REF.kowalewski.2018.1503" rid="brca1.REF.kowalewski.2018.1503">Kowalewski et al 2018</a>].</p><p><b>Melanoma.</b> The risk for melanomas of both the skin and eyes is elevated in individuals with a <i>BRCA2</i> pathogenic variant [<a class="bibr" href="#brca1.REF.breast_cancer_linkage_consortium.1999.1310" rid="brca1.REF.breast_cancer_linkage_consortium.1999.1310">Breast Cancer Linkage Consortium 1999</a>, <a class="bibr" href="#brca1.REF.hearle.2003.458" rid="brca1.REF.hearle.2003.458">Hearle et al 2003</a>, <a class="bibr" href="#brca1.REF.van_asperen.2005.711" rid="brca1.REF.van_asperen.2005.711">van Asperen et al 2005</a>, <a class="bibr" href="#brca1.REF.gumaste.2015.1498" rid="brca1.REF.gumaste.2015.1498">Gumaste et al 2015</a>]. An analysis of 490 families with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants showed an increased risk for uveal melanoma in individuals with germline <i>BRCA2</i> pathogenic variants [<a class="bibr" href="#brca1.REF.moran.2012.235" rid="brca1.REF.moran.2012.235">Moran et al 2012</a>].</p><p><b>Other cancers.</b> Individuals with <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants may be at a higher risk for additional malignancies. Furthermore, women with a <i>BRCA1</i> pathogenic variant may have an elevated risk for serous uterine cancer, but the data are not conclusive [<a class="bibr" href="#brca1.REF.de_jonge.2017.215" rid="brca1.REF.de_jonge.2017.215">de Jonge et al 2017</a>].</p><p>No associated benign tumors or physical abnormalities are presently known to be associated with pathogenic variants in <i>BRCA1</i> or <i>BRCA2</i>.</p></div><div id="brca1.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><p>Ovarian cancer and primary papillary serous carcinoma of the peritoneum are considerably more common and tend to develop at an earlier age in women with a germline <i>BRCA1</i> pathogenic variant as compared to women with a germline <i>BRCA2</i> pathogenic variant [<a class="bibr" href="#brca1.REF.casey.2005.457" rid="brca1.REF.casey.2005.457">Casey et al 2005</a>, <a class="bibr" href="#brca1.REF.yates.2011.463" rid="brca1.REF.yates.2011.463">Yates et al 2011</a>]. Those with <i>BRCA2</i> pathogenic variants tend to be at greater risk for male breast cancer [<a class="bibr" href="#brca1.REF.evans.2010.710" rid="brca1.REF.evans.2010.710">Evans et al 2010</a>], prostate cancer [<a class="bibr" href="#brca1.REF.mersch.2015.269" rid="brca1.REF.mersch.2015.269">Mersch et al 2015</a>], pancreatic cancer [<a class="bibr" href="#brca1.REF.dagan.2008.267" rid="brca1.REF.dagan.2008.267">Dagan 2008</a>], and melanoma.</p></div><div id="brca1.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p><i>BRCA1</i> and <i>BRCA2</i> genotype-phenotype correlations have been identified. Such correlations are not currently used in individual risk assessment and management but may be in the future with appropriate validation.</p><div id="brca1.BRCA1"><h4>
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<i>BRCA1</i>
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</h4><p><b>p.Arg1699Gln</b> is a reduced-penetrance allele that was determined to be associated with intermediate risk; the estimated cumulative risk to age 70 for breast or ovarian cancer was 24% [<a class="bibr" href="#brca1.REF.spurdle.2012.525" rid="brca1.REF.spurdle.2012.525">Spurdle et al 2012</a>].</p></div><div id="brca1.BRCA2"><h4>
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<i>BRCA2</i>
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</h4><p><b>p.Lys3326Ter</b> was associated with a lower risk of developing breast and ovarian cancer than other <i>BRCA2</i> pathogenic variants in a large case-control study based on an international consortium of individuals; for breast cancer the odds ratio (OR<sub>w</sub>) was 1.28; for invasive ovarian cancer the OR<sub>w</sub> was 1.26 [<a class="bibr" href="#brca1.REF.meeks.2015.djv315" rid="brca1.REF.meeks.2015.djv315">Meeks et al 2015</a>].</p><p>An ovarian cancer cluster region (OCCR) in or near exon 11 in both <i>BRCA1</i> and <i>BRCA2</i> has been identified [<a class="bibr" href="#brca1.REF.rebbeck.2015.1347" rid="brca1.REF.rebbeck.2015.1347">Rebbeck et al 2015</a>]. Pathogenic variants within the OCCR have been associated with a higher ratio of ovarian to breast cancer than is seen in families with a pathogenic variant elsewhere in the genes.</p><p>In <i>BRCA1</i> and <i>BRCA2</i>, multiple breast cancer cluster regions have been observed and are associated with relatively elevated breast cancer risk and lower ovarian cancer risk [<a class="bibr" href="#brca1.REF.rebbeck.2015.1347" rid="brca1.REF.rebbeck.2015.1347">Rebbeck et al 2015</a>].</p></div></div><div id="brca1.Penetrance"><h3>Penetrance</h3><p>The penetrance of breast, ovarian, and other cancers associated with pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> is less than 100% (see <a href="/books/NBK1247/table/brca1.T.risk_of_malignancy_in_individual/?report=objectonly" target="object" rid-ob="figobbrca1Triskofmalignancyinindividual">Table 2</a>).</p></div><div id="brca1.Prevalence"><h3>Prevalence</h3><p><i>BRCA1</i> and <i>BRCA2</i> pathogenic variants are the most common cause of HBOC. The prevalence of <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants in the general population is estimated at 1:400 to 1:500 [<a class="bibr" href="#brca1.REF.anglian_breast_cancer_study_group.2000.1301" rid="brca1.REF.anglian_breast_cancer_study_group.2000.1301">Anglian Breast Cancer Study Group 2000</a>, <a class="bibr" href="#brca1.REF.whittemore.2004.2078" rid="brca1.REF.whittemore.2004.2078">Whittemore et al 2004</a>].</p><p>The prevalence of <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC is increased in certain populations due to founder variants (see <a href="/books/NBK1247/table/brca1.T.brca1_and_brca2associated_heredi/?report=objectonly" target="object" rid-ob="figobbrca1Tbrca1andbrca2associatedheredi">Table 6</a>):</p><ul><li class="half_rhythm"><div>Individuals of Ashkenazi Jewish descent: prevalence of 1:40 [<a class="bibr" href="#brca1.REF.struewing.1997.1401" rid="brca1.REF.struewing.1997.1401">Struewing et al 1997</a>, <a class="bibr" href="#brca1.REF.gabaikapara.2014.14205" rid="brca1.REF.gabaikapara.2014.14205">Gabai-Kapara et al 2014</a>]</div></li><li class="half_rhythm"><div>Inuit from Ammassalik (Greenland): prevalence of 1:10 to 1:100 [<a class="bibr" href="#brca1.REF.hansen.2009.69" rid="brca1.REF.hansen.2009.69">Hansen et al 2009</a>, <a class="bibr" href="#brca1.REF.harboe.2009.413" rid="brca1.REF.harboe.2009.413">Harboe et al 2009</a>, <a class="bibr" href="#brca1.REF.hansen.2010.259" rid="brca1.REF.hansen.2010.259">Hansen et al 2010</a>]</div></li></ul><p>Founder variants in <i>BRCA1</i> and/or <i>BRCA2</i> have also been reported in several additional populations, including individuals of African, Amish, and Icelandic ancestry (see <a href="/books/NBK1247/table/brca1.T.brca1_and_brca2associated_heredi/?report=objectonly" target="object" rid-ob="figobbrca1Tbrca1andbrca2associatedheredi">Table 6</a>).</p></div></div><div id="brca1.Genetically_Related_Allelic_Disord"><h2 id="_brca1_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p><a href="/books/n/gene/fa/?report=reader"><b>Fanconi anemia.</b></a> Biallelic germline pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> are associated with Fanconi anemia. Fanconi anemia is characterized by developmental abnormalities in major organ systems, early-onset bone marrow failure with pancytopenia (often in the first decade of life), and a high predisposition to cancer, including early-onset acute leukemia and solid tumors with a cumulative probability of any malignancy of 97% by age six years.</p></div><div id="brca1.Differential_Diagnosis"><h2 id="_brca1_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Syndromic breast cancer.</b> Individuals with the following cancer susceptibility syndromes have an elevated breast cancer risk. In many instances, <i>BRCA1</i>- and <i>BRCA2</i>-associated hereditary breast and ovarian cancer (HBOC) can be distinguished from these other disorders based on the constellation of tumors present in the family; however, in some cases, molecular genetic testing may be necessary to differentiate the disorders.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Tgenesassociatedwithcancersus"><a href="/books/NBK1247/table/brca1.T.genes_associated_with_cancer_sus/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobbrca1Tgenesassociatedwithcancersus"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.genes_associated_with_cancer_sus"><a href="/books/NBK1247/table/brca1.T.genes_associated_with_cancer_sus/?report=objectonly" target="object" rid-ob="figobbrca1Tgenesassociatedwithcancersus">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes Associated with Cancer Susceptibility to Consider in the Differential Diagnosis of <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer </p></div></div></div><div id="brca1.Management"><h2 id="_brca1_Management_">Management</h2><div id="brca1.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>Individuals who have a germline pathogenic variant in <i>BRCA1</i> or <i>BRCA2</i> are counseled at the time of disclosure of molecular genetic test results about their options for <a href="#brca1.Surveillance">Surveillance</a> and <a href="#brca1.Prevention_of_Primary_Manifestatio">Prevention of Primary Manifestations</a>.</p></div><div id="brca1.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p><b>Breast cancer.</b> National Comprehensive Cancer Network (NCCN) guidelines suggest that women with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant could consider bilateral mastectomy as a primary surgical treatment of breast cancer because of their elevated rate of ipsilateral and contralateral breast cancer (<a href="https://www.nccn.org/professionals/physician_gls/default.aspx#detection" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCCN Guidelines</a>; no-fee registration and login required).</p><p>PARP inhibitors have emerged as a promising treatment in individuals with <i>BRCA1</i>- and <i>BRCA2</i>-associated breast cancer, given their role in DNA repair. Because <i>BRCA1</i>, <i>BRCA2</i>, and PARP participate in DNA repair, their mutual disruption could lead to "synergistic lethality" of tumor cells. PARP inhibitors were first studied in women with <i>BRCA1</i>- and <i>BRCA2</i>-associated metastatic breast cancer. Significant improvement was seen in in progression-free survival, leading to FDA approval of olaparib for women with locally advanced metastatic breast cancer in 2017 [<a class="bibr" href="#brca1.REF.robson.2017.523" rid="brca1.REF.robson.2017.523">Robson et al 2017</a>, <a class="bibr" href="#brca1.REF.litton.2018.753" rid="brca1.REF.litton.2018.753">Litton et al 2018</a>]. In a recent randomized, double-blind Phase III trial, olaparib also improved progression-free survival in individuals with early, high-risk, human epidermal growth factor receptor 2-negative <i>BRCA1</i>- and <i>BRCA2</i>-associated breast cancer in the adjuvant setting [<a class="bibr" href="#brca1.REF.tutt.2021.2394" rid="brca1.REF.tutt.2021.2394">Tutt et al 2021</a>].</p><p><b>Ovarian cancer.</b> PARP inhibitors were first found to improve response rates in the setting of ovarian cancer recurrence after failure of platinum-based therapies [<a class="bibr" href="#brca1.REF.fong.2009.123" rid="brca1.REF.fong.2009.123">Fong et al 2009</a>]. Olaparib has subsequently shown significantly improved progression-free survival in platinum-sensitive recurrent ovarian cancer as maintenance therapy. In this study, individuals with <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants showed the most benefit [<a class="bibr" href="#brca1.REF.ledermann.2014.852" rid="brca1.REF.ledermann.2014.852">Ledermann et al 2014</a>]. Olaparib has also demonstrated significant benefit as maintenance therapy in women with newly diagnosed disease in advanced <i>BRCA1</i>- and <i>BRCA2</i>-associated ovarian cancer following primary therapy. In the SOLO-1 trial, women randomized to olaparib maintenance treatment had a 70% lower risk of disease progression or death compared to the placebo [<a class="bibr" href="#brca1.REF.moore.2018.2495" rid="brca1.REF.moore.2018.2495">Moore et al 2018</a>]. Olaparib was given FDA approval for metastatic ovarian cancer in 2014, for maintenance therapy for recurrent disease in 2017, and for maintenance therapy after completion of adjuvant therapy in 2019.</p><p><b>Prostate cancer.</b> After promising Phase I data on the use of olaparib in solid tumors, a Phase II study established its activity in men with <i>BRCA1</i>- and <i>BRCA2</i>-associated advanced prostate cancer [<a class="bibr" href="#brca1.REF.kaufman.2015.244" rid="brca1.REF.kaufman.2015.244">Kaufman et al 2015</a>]. A subsequent Phase II trial compared olaparib to androgen targeted therapy plus prednisone in men with progressive prostate cancer who had pathogenic variants in DNA damage repair genes, including <i>BRCA1</i> and <i>BRCA2</i>. A significant improvement in response rate and disease-free survival was seen in the olaparib treatment group. Both olaparib and rucaparib were approved by the FDA in 2020 for use in this setting [<a class="bibr" href="#brca1.REF.de_bono.2020.2091" rid="brca1.REF.de_bono.2020.2091">De Bono et al 2020</a>].</p><p><b>Pancreatic cancer.</b> The poor response of pancreatic cancer to standard systemic therapies has intensified the search for novel targeted agents. The Phase III POLO trial randomized individuals with <i>BRCA1</i>- and <i>BRCA2</i>-associated metastatic pancreatic cancer to olaparib vs placebo. Response rates were 22.1% in the olaparib group and 9.6% in the placebo group. Both progression-free survival and overall survival were doubled in the olaparib group. Toxicities, especially when a PARP inhibitor is combined with other systemic therapy, however, limit its use. The FDA has approved olaparib as maintenance therapy for <i>BRCA1</i>- and <i>BRCA2</i>-associated advanced pancreatic cancer.</p><p><b>Melanoma.</b> Treatment is per dermatologist and/or oncologist.</p></div><div id="brca1.Prevention_of_Primary_Manifestatio"><h3>Prevention of Primary Manifestations</h3><p>
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<b>Breast cancer</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">Consider prophylactic bilateral mastectomy.</div></li><li class="half_rhythm"><div class="half_rhythm">Given the conflicting data on the degree of risk reduction of breast cancer associated with prophylactic oophorectomy, consider discussing the risks and benefits of this approach with a genetics specialist.</div></li><li class="half_rhythm"><div class="half_rhythm">Chemoprevention. In a retrospective study tamoxifen reduced the risk for breast cancer by 62% among healthy women with a <i>BRCA2</i> germline variant [<a class="bibr" href="#brca1.REF.king.2001.2251" rid="brca1.REF.king.2001.2251">King et al 2001</a>]. The sample size, however, was extremely small. There have been no prospective randomized trials of tamoxifen as a chemoprevention agent specifically in women with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants. Several studies, however, have found a significant protective effect of tamoxifen on the risk of contralateral breast cancer in women with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants. Risk reduction in these studies ranged from 50% to 69%. These studies are limited by their retrospective case-control designs [<a class="bibr" href="#brca1.REF.gronwald.2006.2281" rid="brca1.REF.gronwald.2006.2281">Gronwald et al 2006</a>, <a class="bibr" href="#brca1.REF.pierce.2006.2437" rid="brca1.REF.pierce.2006.2437">Pierce et al 2006</a>, <a class="bibr" href="#brca1.REF.phillips.2013.3091" rid="brca1.REF.phillips.2013.3091">Phillips et al 2013</a>].</div><div class="half_rhythm">Note: Significant adverse consequences of tamoxifen treatment included higher rates of endometrial cancer and thromboembolic episodes (including pulmonary embolism) in those individuals who took the medication than in those who did not. Women with a history of thromboembolic disease or with a coagulation disorder should avoid taking tamoxifen. Women on tamoxifen should be counseled to report any abnormal vaginal bleeding immediately to their gynecologist.</div></li><li class="half_rhythm"><div class="half_rhythm">Breast feeding for a cumulative total of more than one year reduced the risk for breast cancer [<a class="bibr" href="#brca1.REF.jernstr_m.2004.1094" rid="brca1.REF.jernstr_m.2004.1094">Jernström et al 2004</a>].</div></li></ul><p>
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<b>Ovarian cancer (including fallopian tube cancer)</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">Consider prophylactic salpingo-oophorectomy, recognizing that completion of childbearing may factor into this decision. A prospective cohort study of 2,482 women with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants reported a 79% reduction in ovarian cancer mortality and a 60% reduction on all-cause mortality associated with risk-reducing oophorectomy [<a class="bibr" href="#brca1.REF.marchetti.2014.150" rid="brca1.REF.marchetti.2014.150">Marchetti et al 2014</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">With the realization that the fallopian tube is frequently the site of serous ovarian cancer and its precursor lesions, a new paradigm of prophylactic salpingectomy after childbearing followed by delayed oophorectomy at the time of menopause has been suggested. While theoretically offering protection against ovarian cancer, this approach would also avoid the adverse consequences of premature menopause. Currently studies are under way to determine its feasibility, safety, and efficacy [<a class="bibr" href="#brca1.REF.swanson.2016.20" rid="brca1.REF.swanson.2016.20">Swanson & Bakkum-Gamez 2016</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">Tubal ligation. A meta-analysis of 13 studies showed a reduction in risk for ovarian cancer of 34% in the general population after tubal ligation [<a class="bibr" href="#brca1.REF.cibula.2011.55" rid="brca1.REF.cibula.2011.55">Cibula et al 2011</a>]. In a meta-analysis of modifiers of risk of cancer in individuals with pathogenic variants in <i>BRCA1</i> or <i>BRCA2,</i> tubal ligation was associated with a reduced risk of ovarian cancer in females with a <i>BRCA1</i> pathogenic variant, although study design issues limit the impact of these findings [<a class="bibr" href="#brca1.REF.friebel.2014.dju091" rid="brca1.REF.friebel.2014.dju091">Friebel et al 2014</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">A meta-analysis of 18 studies including 13,677 women with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants found a 50% reduction in risk of ovarian cancer associated with oral contraceptive use [<a class="bibr" href="#brca1.REF.iodice.2010.2275" rid="brca1.REF.iodice.2010.2275">Iodice et al 2010</a>]. The maximum benefit of oral contraceptives is obtained with three to six years of use [<a class="bibr" href="#brca1.REF.kotsopoulos.2015.1136" rid="brca1.REF.kotsopoulos.2015.1136">Kotsopoulos et al 2015</a>].</div><div class="half_rhythm">Note: There is no evidence that use of current (after 1975) oral contraceptive formulations increases the risk for early-onset breast cancer for women with a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</div></li></ul></div><div id="brca1.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Trecommendedsurveillanceforwom"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_wom/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobbrca1Trecommendedsurveillanceforwom"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.recommended_surveillance_for_wom"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_wom/?report=objectonly" target="object" rid-ob="figobbrca1Trecommendedsurveillanceforwom">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Women with <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Trecommendedsurveillanceformen"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_men/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobbrca1Trecommendedsurveillanceformen"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.recommended_surveillance_for_men"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_men/?report=objectonly" target="object" rid-ob="figobbrca1Trecommendedsurveillanceformen">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Men with <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer </p></div></div></div><div id="brca1.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>No data specific to individuals with <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants are available.</p></div><div id="brca1.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>Once a cancer-predisposing <i>BRCA1</i> or <i>BRCA2</i> germline variant has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial variant and thus need increased surveillance and specific treatments when a cancer is identified.</p><p>See <a href="#brca1.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="brca1.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Several ongoing studies are investigating novel approaches to the treatment of <i>BRCA1</i>- and <i>BRCA2</i>-associated breast and ovarian cancer. The majority of these studies involve PARP inhibitors.</p><p>Several prospective and randomized clinical trials are investigating PARP inhibitor treatment of metastatic pancreatic cancer [<a class="bibr" href="#brca1.REF.chi.2021.17562848211014818" rid="brca1.REF.chi.2021.17562848211014818">Chi et al 2021</a>, <a class="bibr" href="#brca1.REF.macchini.2021.102262" rid="brca1.REF.macchini.2021.102262">Macchini et al 2021</a>].</p><p>Studies to identify biomarkers of disease resistance and expected treatment toxicity are also under way [<a class="bibr" href="#brca1.REF.jeong.2021.3509" rid="brca1.REF.jeong.2021.3509">Jeong & Park 2021</a>].</p><p>Additional clinical trials are exploring the use of other PARP inhibitors alone or in combination with other systemic treatments.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies.</p></div><div id="brca1.Other"><h3>Other</h3><p><b>Hormone replacement therapy (HRT).</b> General population studies suggest that long-term estrogen replacement therapy in postmenopausal women may increase breast cancer risk, but that short-term use to treat menopausal symptoms does not. However, even relatively short-term combined estrogen plus progestin use was shown to increase the incidence of breast cancers in a randomized, placebo-controlled trial of HRT [<a class="bibr" href="#brca1.REF.chlebowski.2003.3243" rid="brca1.REF.chlebowski.2003.3243">Chlebowski et al 2003</a>].</p><p>Three observational studies on the impact of HRT on breast cancer risk in <i>BRCA 1</i> and <i>BRCA2</i> heterozygotes have been published. <a class="bibr" href="#brca1.REF.rebbeck.2005.7804" rid="brca1.REF.rebbeck.2005.7804">Rebbeck et al [2005]</a> evaluated breast cancer risk associated with HRT after bilateral prophylactic oophorectomy in a cohort of 462 women with a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant and found that HRT of any type after bilateral prophylactic oophorectomy did not significantly alter the reduction in breast cancer risk associated with the surgery. The postoperative follow up was 3.6 years. It was concluded that short-term HRT does not substantially increase the risk for breast cancer in women with a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant. A subsequent study of expanded data from this cohort included 1,299 women with a mean follow up of 5.4 years. There was no increase in breast cancer risk, and a significant decrease in breast cancer risk was found among <i>BRCA1</i> heterozygotes [<a class="bibr" href="#brca1.REF.domchek.2011" rid="brca1.REF.domchek.2011">Domchek et al 2011</a>]. In another matched case-control study of 472 postmenopausal women with a <i>BRCA1</i> pathogenic variant, the use of HRT was associated with a reduction in breast cancer risk [<a class="bibr" href="#brca1.REF.eisen.2008.1361" rid="brca1.REF.eisen.2008.1361">Eisen et al 2008</a>]. Finally, a case-control study of 432 matched pairs with a mean follow up of 4.3 years also found a decrease in the risk for breast cancer in <i>BRCA1</i> heterozygotes [<a class="bibr" href="#brca1.REF.kotsopoulos.2016.365" rid="brca1.REF.kotsopoulos.2016.365">Kotsopoulos et al 2016</a>]. Taken together, these studies support the short-term use of HRT among <i>BRCA1</i> and <i>BRCA2</i> heterozygotes who have undergone surgical menopause.</p></div></div><div id="brca1.Genetic_Counseling"><h2 id="_brca1_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="brca1.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>BRCA1-</i> and <i>BRCA2-</i>associated hereditary breast and ovarian cancer (HBOC) is inherited in an autosomal dominant manner.</p></div><div id="brca1.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant</b>
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</p><ul><li class="half_rhythm"><div>The vast majority of individuals with a germline pathogenic variant in <i>BRCA1</i> or <i>BRCA2</i> inherited it from a parent. The parent with the pathogenic variant may or may not have had a cancer diagnosis depending on the following variables:</div><ul><li class="half_rhythm"><div>Penetrance of the variant</div></li><li class="half_rhythm"><div>Sex of the parent</div></li><li class="half_rhythm"><div>Age of the parent</div></li><li class="half_rhythm"><div>Cancer risk reduction in the parent as a result of screening or prophylactic surgeries</div></li><li class="half_rhythm"><div>Early death of the parent</div></li></ul></li><li class="half_rhythm"><div>It is appropriate to offer molecular genetic testing to both parents of an individual with a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant to determine which side of the family is at risk. Generally, the pattern of cancers seen in the family guides which parent is tested first.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The proband has a <i>de novo</i> pathogenic variant. <i>De novo</i> variants have been rarely reported (≤5%) [<a class="bibr" href="#brca1.REF.golmard.2016.1324" rid="brca1.REF.golmard.2016.1324">Golmard et al 2016</a>, <a class="bibr" href="#brca1.REF.antonucci.2017.238" rid="brca1.REF.antonucci.2017.238">Antonucci et al 2017</a>].</div></li><li class="half_rhythm"><div>The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism [<a class="bibr" href="#brca1.REF.alhopuro.2020.307" rid="brca1.REF.alhopuro.2020.307">Alhopuro et al 2020</a>]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ cells only.</div></li></ul></li><li class="half_rhythm"><div>An apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband</b>
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<b>with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</b> The risk to full sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If one parent has the <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant identified in the proband, the risk that a sib will inherit the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>The risk of developing cancer in a sib who inherits the familial <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant depends on numerous variables including the penetrance of the pathogenic variant and the sex and age of the heterozygous sib.</div></li></ul><p>
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<b>Offspring of a proband with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant</b>
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</p><ul><li class="half_rhythm"><div>The offspring of an individual identified as having a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant have a 50% chance of inheriting the pathogenic variant.</div></li><li class="half_rhythm"><div>The risk of developing cancer in offspring who inherit the <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant depends on numerous variables including the penetrance of the pathogenic variant and the sex and age of the heterozygous individual.</div></li></ul><p><b>Other family members of a proband with a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</b> The risk to other family members depends on the genetic status of the proband's parents. If a parent has a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant, the parent's family members are at risk. Their exact risk depends on their biological relationship with the proband.</p></div><div id="brca1.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#brca1.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for the determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul><p><b>Genetic cancer risk assessment and counseling.</b> For a comprehensive description of the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without molecular genetic testing, see <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/risk-assessment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cancer Genetics Risk Assessment and Counseling – for health professionals</a> (part of PDQ<sup>®</sup>, National Cancer Institute).</p><p><b>At-risk asymptomatic adult relatives.</b> In general, relatives of an individual who has a <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant should be counseled regarding their risk of having inherited the same variant, their options for molecular genetic testing, their cancer risk, and recommendations for cancer screening (see <a href="#brca1.Surveillance">Surveillance</a>) and prophylactic surgery (see <a href="#brca1.Prevention_of_Primary_Manifestatio">Prevention of Primary Manifestations</a>).</p><p>At-risk adult relatives who have not inherited the cancer-predisposing germline variant identified in the proband are presumed to be at or above the general population risk of developing cancer, depending on personal risk factors. For example, a female at-risk relative who does not have the family-specific <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant may still be at an elevated risk for breast cancer based on a breast biopsy history that revealed atypical ductal hyperplasia.</p><p>For family members determined to be at general population risk of developing cancer, appropriate cancer screening such as that recommended by the <a href="https://www.cancer.org/cancer/breast-cancer.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">American Cancer Society</a> or the <a href="https://www.nccn.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">National Comprehensive Cancer Network</a> (NCCN) for individuals of average risk is recommended. Note: This presumption cannot apply to individuals who did not have an identifiable <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant if the affected individual in the family either has not undergone molecular genetic testing of <i>BRCA1</i> or <i>BRCA2</i> or did not have an identified <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant.</p><p><b>Testing of asymptomatic individuals younger than age 18 years.</b> In general, genetic testing for <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC is not recommended for at-risk individuals younger than age 18 years. Guidelines established jointly by the American College of Medical Genetics and the American Society of Human Genetics state that predictive genetic testing should only be performed in individuals younger than age 18 years when it will affect their medical management. <a href="#brca1.Surveillance">Surveillance</a> for <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC is typically recommended to begin at approximately age 25, which is why it is recommended that the decision to test be postponed until an individual reaches adulthood and can make an independent decision. It is important to note, however, that since there are rare reports of individuals with <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC diagnosed with cancer at very young ages, it is recommended that screening be individualized based on the earliest diagnosis in the family.</p><p>For more information, see the National Society of Genetic Counselors <a href="https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for-adult-onset-conditions" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">position statement</a> on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics <a href="https://pediatrics.aappublications.org/content/131/3/620.full.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">policy statement</a>: ethical and policy issues in genetic testing and screening of children.</p></div><div id="brca1.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>BRCA1</i> or <i>BRCA2</i> germline pathogenic variant has been identified in the family, prenatal and preimplantation genetic testing for <i>BRCA1</i>- and <i>BRCA2</i>-associated HBOC are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful. For more information, see the National Society of Genetic Counselors <a href="https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/prenatal-testing-for-adult-onset-conditions-1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Position Statement</a> on prenatal testing in adult-onset conditions.</p></div></div><div id="brca1.Resources"><h2 id="_brca1_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>Breast Cancer Information Core</b>
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</div><div>
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<i>Breast cancer resources</i>
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</div><div>National Human Genome Research Institute (NHGRI)</div><div>
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<a href="http://research.nhgri.nih.gov/bic/resources.shtml" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">research.nhgri.nih.gov/bic/resources.shtml</a>
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</div></li><li class="half_rhythm"><div>
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<b>Bright Pink</b>
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</div><div>670 North Clark Street</div><div>Suite 2</div><div>Chicago IL 60654</div><div>
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<a href="http://www.brightpink.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.brightpink.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Gilda's Club Worldwide</b>
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</div><div>48 Wall Street</div><div>11th Floor</div><div>New York NY 10005</div><div><b>Phone:</b> 888-445-3248 (toll-free)</div><div><b>Fax:</b> 917-305-0549</div><div><b>Email:</b> info@gildasclub.org</div><div>
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<a href="http://www.cancersupportcommunity.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.cancersupportcommunity.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Breast Cancer Coalition (NBCC)</b>
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</div><div><b>Phone:</b> 800-622-2838</div><div><b>Fax:</b> 202-314-3458</div><div><b>Email:</b> info@stopbreastcancer.org</div><div>
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<a href="http://www.stopbreastcancer.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.stopbreastcancer.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Cancer Institute (NCI)</b>
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</div><div><b>Phone:</b> 800-4-CANCER</div><div><b>Email:</b> NCIinfo@nih.gov</div><div>
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<a href="http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Genetics of Breast and Ovarian Cancer (PDQ)</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Cancer Institute (NCI)</b>
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</div><div>6116 Executive Boulevard</div><div>Suite 300</div><div>Bethesda MD 20892-8322</div><div><b>Phone:</b> 800-422-6237 (toll-free)</div><div><b>Email:</b> cancergovstaff@mail.nih.gov</div><div>
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<a href="http://www.cancer.gov/cancertopics/types/breast" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast Cancer</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Ovarian Cancer Coalition (NOCC)</b>
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</div><div>2501 Oak Lawn Avenue</div><div>Suite 435</div><div>Dallas TX 75219</div><div><b>Phone:</b> 888-682-7426 (Toll-free Helpline); 214-273-4200</div><div><b>Fax:</b> 214-273-4201</div><div><b>Email:</b> nocc@ovarian.org</div><div>
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<a href="http://www.ovarian.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ovarian.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>NCBI Genes and Disease</b>
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</div><div>
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<a href="/books/NBK22168/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast and ovarian cancer</a>
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</div></li><li class="half_rhythm"><div>
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<b>Probability of Breast Cancer in American Women</b>
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</div><div>National Cancer Institute Public Inquiries Office</div><div>6116 Executive Boulevard</div><div>Suite 300</div><div>Bethesda MD 20892-8322</div><div><b>Phone:</b> 800-422-6237 (toll-free)</div><div><b>Email:</b> cancergovstaff@mail.nih.gov</div><div>
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<a href="http://www.cancer.gov/cancertopics/factsheet/Detection/probability-breast-cancer" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Probability of Breast Cancer in American Women</a>
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</div></li><li class="half_rhythm"><div>
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<b>Sharsheret</b>
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</div><div><b>Phone:</b> 866-474-2774</div><div><b>Email:</b> info@sharsheret.org</div><div>
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<a href="http://www.sharsheret.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.sharsheret.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Susan G. Komen Breast Cancer Foundation</b>
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</div><div><b>Phone:</b> 877 GO KOMEN</div><div><b>Email:</b> helpline@komen.org</div><div>
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<a href="http://www.komen.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.komen.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>American Cancer Society</b>
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</div><div><b>Phone:</b> 800-227-2345</div><div>
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<a href="http://www.cancer.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">cancer.org</a>
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</div></li><li class="half_rhythm"><div>
|
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<b>CancerCare</b>
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</div><div><b>Phone:</b> 800-813-4673</div><div><b>Email:</b> info@cancercare.org</div><div>
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<a href="http://www.cancercare.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">cancercare.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>FORCE</b>
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</div><div>
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<i>A discussion forum specifically for women who are at a high risk of developing ovarian cancer or breast cancer</i>
|
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</div><div>Facing Hereditary Cancer Empowered</div><div><b>Phone:</b> 866-288-7475</div><div><b>Email:</b> info@facingourrisk.org</div><div>
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<a href="http://www.facingourrisk.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">facingourrisk.org</a>
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</div></li><li class="half_rhythm"><div>
|
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<b>National Cancer Institute (NCI)</b>
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</div><div><b>Phone:</b> 800-422-6237</div><div><b>Email:</b> NCIinfo@nih.gov</div><div>
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<a href="http://www.cancer.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">cancer.gov</a>
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</div></li><li class="half_rhythm"><div>
|
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<b>National Coalition for Cancer Survivorship (NCCS)</b>
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</div><div><b>Phone:</b> 877-NCCS-YES</div><div><b>Email:</b> info@canceradvocacy.org</div><div>
|
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<a href="http://www.canceradvocacy.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">canceradvocacy.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Familial Ovarian Cancer Registry</b>
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</div><div>Roswell Park Cancer Institute</div><div>Elm and Carlton Streets</div><div>Buffalo NY 14263</div><div><b>Phone:</b> 716-845-4503</div><div>
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<a href="http://ovariancancer.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ovariancancer.com</a>
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</div></li></ul>
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</div><div id="brca1.Molecular_Genetics"><h2 id="_brca1_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1molgenTA"><a href="/books/NBK1247/table/brca1.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobbrca1molgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.molgen.TA"><a href="/books/NBK1247/table/brca1.molgen.TA/?report=objectonly" target="object" rid-ob="figobbrca1molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1molgenTB"><a href="/books/NBK1247/table/brca1.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobbrca1molgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.molgen.TB"><a href="/books/NBK1247/table/brca1.molgen.TB/?report=objectonly" target="object" rid-ob="figobbrca1molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer (View All in OMIM) </p></div></div><div id="brca1.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>BRCA1</i> encodes breast cancer type 1 susceptibility protein (BRCA1), a phosphoprotein normally located in the nucleus [<a class="bibr" href="#brca1.REF.chen.1996.3168" rid="brca1.REF.chen.1996.3168">Chen et al 1996</a>]. BRCA1 interacts with several proteins involved in cellular pathways, including cell-cycle progression, gene transcription regulation, DNA damage response, and ubiquitination [<a class="bibr" href="#brca1.REF.deng.2006.1416" rid="brca1.REF.deng.2006.1416">Deng 2006</a>, <a class="bibr" href="#brca1.REF.rosen.2006.175" rid="brca1.REF.rosen.2006.175">Rosen et al 2006</a>].</p><p>The BRCA1/BARD1 protein complex enhances ubiquitin ligase activity, which is associated with the regulation of centrosome function and involved in DNA repair and cell cycle regulation [<a class="bibr" href="#brca1.REF.bork.1997.68" rid="brca1.REF.bork.1997.68">Bork et al 1997</a>, <a class="bibr" href="#brca1.REF.callebaut.1997.25" rid="brca1.REF.callebaut.1997.25">Callebaut & Mornon 1997</a>, <a class="bibr" href="#brca1.REF.sankaran.2006.4100" rid="brca1.REF.sankaran.2006.4100">Sankaran et al 2006</a>].</p><p>BRCA1 colocalizes with BRCA2 and RAD51 at sites of DNA damage and activates RAD51-mediated homologous recombination repair of DNA double-strand breaks [<a class="bibr" href="#brca1.REF.cousineau.2005.11384" rid="brca1.REF.cousineau.2005.11384">Cousineau et al 2005</a>]. BRCA2 regulates the availability and activity of RAD51, which coats single-strand DNA to form a nucleoprotein filament that invades and pairs with a homologous DNA duplex to initiate strand exchange [<a class="bibr" href="#brca1.REF.venkitaraman.2002.171" rid="brca1.REF.venkitaraman.2002.171">Venkitaraman 2002</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbrca1Tbrca1andbrca2associatedheredi"><a href="/books/NBK1247/table/brca1.T.brca1_and_brca2associated_heredi/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobbrca1Tbrca1andbrca2associatedheredi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="brca1.T.brca1_and_brca2associated_heredi"><a href="/books/NBK1247/table/brca1.T.brca1_and_brca2associated_heredi/?report=objectonly" target="object" rid-ob="figobbrca1Tbrca1andbrca2associatedheredi">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>BRCA1</i>- and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer: Notable Pathogenic Variants by Gene </p></div></div></div></div><div id="brca1.Chapter_Notes"><h2 id="_brca1_Chapter_Notes_">Chapter Notes</h2><div id="brca1.Author_History"><h3>Author History</h3><p>Julie O Bars Culver, MS; Fred Hutchinson Cancer Research Center (1998-2011) <br />Wylie Burke, MD, PhD; University of Washington (1998-2005) <br />Mary B Daly, MD, PhD (1998-present) <br />Gerald L Feldman, MD, PhD; Wayne State University School of Medicine (2002-2016) <br />Judith L Hull, MS; Memorial Sloan-Kettering Cancer Center (1998-2005) <br />Ephrat Levy-Lahad, MD; Sharre Zedek Medical Center (1998-2007) <br />Tuya Pal, MD (2016-present)<br />Nancie Petrucelli, MS (2002-present)</p></div><div id="brca1.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>21 September 2023 (np,sw) Revision: information about cancer risk in individuals who are heterozygous for a pathogenic variant in <i>ATM</i> added to <a href="#brca1.Differential_Diagnosis">Differential Diagnosis</a></div></li><li class="half_rhythm"><div>26 May 2022 (mbd,tp) Revision: recommended surveillance for ovarian and pancreatic cancer (<a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_wom/?report=objectonly" target="object" rid-ob="figobbrca1Trecommendedsurveillanceforwom">Tables 4</a> and <a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_men/?report=objectonly" target="object" rid-ob="figobbrca1Trecommendedsurveillanceformen">5</a>)</div></li><li class="half_rhythm"><div>3 February 2022 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>15 December 2016 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>26 September 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>20 January 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>19 June 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 December 2005 (cd) Revision: Differential Diagnosis</div></li><li class="half_rhythm"><div>3 September 2004 (jbc) Revision: Genetically Related Disorders</div></li><li class="half_rhythm"><div>29 March 2004 (ca) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 March 2000 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 September 1998 (pb) Review posted live</div></li><li class="half_rhythm"><div>January 1998 (jbc) Original submission</div></li></ul></div></div><div id="brca1.References"><h2 id="_brca1_References_">References</h2><div id="brca1.Published_Guidelines__Consensus_St"><h3>Published Guidelines / Consensus Statements</h3><ul class="simple-list"><li class="half_rhythm"><div>Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available <a href="https://pediatrics.aappublications.org/content/131/3/620.full.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">online</a>. 2013. Accessed 8-25-23.</div></li><li class="half_rhythm"><div>National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Cancer. Available <a href="https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1503" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">online</a>; no-fee registration and login required. Accessed 8-25-23.</div></li><li class="half_rhythm"><div>National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset conditions. Available <a href="https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for-adult-onset-conditions" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">online</a>. 2018. Accessed 8-25-23.</div></li><li class="half_rhythm"><div>Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL, Lipkin SM, Syngal S, Wollins DS, Lindor NM. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33:3660-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/26324357/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubMed</a>]</div></li></ul></div><div id="brca1.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.alhopuro.2020.307">Alhopuro
|
|
P, Vainionpää
|
|
R, Anttonen
|
|
AK, Aittomäki
|
|
K, Nevanlinna
|
|
H, Pöyhönen
|
|
M. Constitutional mosaicism for a BRCA2 mutation as a cause of early-onset breast cancer.
|
|
Fam Cancer.
|
|
2020;19:307-10.
|
|
[<a href="/pmc/articles/PMC7497290/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497290</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32468491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32468491</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.alsop.2012.2654">Alsop
|
|
K, Fereday
|
|
S, Meldrum
|
|
C, deFazio
|
|
A, Emmanuel
|
|
C, George
|
|
J, Dobrovic
|
|
A, Birrer
|
|
MJ, Webb
|
|
PM, Stewart
|
|
C, Friedlander
|
|
M, Fox
|
|
S, Bowtell
|
|
D, Mitchell
|
|
G. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.
|
|
J Clin Oncol.
|
|
2012;30:2654-63.
|
|
[<a href="/pmc/articles/PMC3413277/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3413277</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22711857" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22711857</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.anglian_breast_cancer_study_group.2000.1301">Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases.
|
|
Br J Cancer.
|
|
2000; 83:1301-8.
|
|
[<a href="/pmc/articles/PMC2408797/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2408797</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11044354" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11044354</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.antoniou.2014.497">Antoniou
|
|
AC, Casadei
|
|
S, Heikkinen
|
|
T, Barrowdale
|
|
D, Pylkäs
|
|
K, Roberts
|
|
J, Lee
|
|
A, Subramanian
|
|
D, De Leeneer
|
|
K, Fostira
|
|
F, Tomiak
|
|
E, Neuhausen
|
|
SL, Teo
|
|
ZL, Khan
|
|
S, Aittomäki
|
|
K, Moilanen
|
|
JS, Turnbull
|
|
C, Seal
|
|
S, Mannermaa
|
|
A, Kallioniemi
|
|
A, Lindeman
|
|
GJ, Buys
|
|
SS, Andrulis
|
|
IL, Radice
|
|
P, Tondini
|
|
C, Manoukian
|
|
S, Toland
|
|
AE, Miron
|
|
P, Weitzel
|
|
JN, Domchek
|
|
SM, Poppe
|
|
B, Claes
|
|
KB, Yannoukakos
|
|
D, Concannon
|
|
P, Bernstein
|
|
JL, James
|
|
PA, Easton
|
|
DF, Goldgar
|
|
DE, Hopper
|
|
JL, Rahman
|
|
N, Peterlongo
|
|
P, Nevanlinna
|
|
H, King
|
|
MC, Couch
|
|
FJ, Southey
|
|
MC, Winqvist
|
|
R, Foulkes
|
|
WD, Tischkowitz
|
|
M. Breast-cancer risk in families with mutations in PALB2.
|
|
N Engl J Med.
|
|
2014;371:497-506.
|
|
[<a href="/pmc/articles/PMC4157599/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4157599</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25099575" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25099575</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.antoniou.2003.1117">Antoniou
|
|
A, Pharoah
|
|
PD, Narod
|
|
S, Risch
|
|
HA, Eyfjord
|
|
JE, Hopper
|
|
JL, Loman
|
|
N, Olsson
|
|
H, Johannsson
|
|
O, Borg
|
|
A, Pasini
|
|
B, Radice
|
|
P, Manoukian
|
|
S, Eccles
|
|
DM, Tang
|
|
N, Olah
|
|
E, Anton-Culver
|
|
H, Warner
|
|
E, Lubinski
|
|
J, Gronwald
|
|
J, Gorski
|
|
B, Tulinius
|
|
H, Thorlacius
|
|
S, Eerola
|
|
H, Nevanlinna
|
|
H, Syrjäkoski
|
|
K, Kallioniemi
|
|
OP, Thompson
|
|
D, Evans
|
|
C, Peto
|
|
J, Lalloo
|
|
F, Evans
|
|
DG, Easton
|
|
DF. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.
|
|
Am J Hum Genet.
|
|
2003;72:1117-30.
|
|
[<a href="/pmc/articles/PMC1180265/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1180265</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12677558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12677558</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.antoniou.2004.1580">Antoniou
|
|
AC, Pharoah
|
|
PP, Smith
|
|
P, Easton
|
|
DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer.
|
|
Br J Cancer.
|
|
2004;91:1580-90.
|
|
[<a href="/pmc/articles/PMC2409934/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2409934</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15381934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15381934</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.antonucci.2017.238">Antonucci
|
|
I, Provenzano
|
|
M, Sorino
|
|
L, Rodrigues
|
|
M, Palka
|
|
G, Stuppia
|
|
L.
|
|
A new case of "de novo" BRCA1 mutation in a patient with early-onset breast cancer.
|
|
Clin Case Rep.
|
|
2017;5:238-40.
|
|
[<a href="/pmc/articles/PMC5331191/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5331191</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28265380" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28265380</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.bahar.2001.440">Bahar
|
|
AY, Taylor
|
|
PJ, Andrews
|
|
L, Proos
|
|
A, Burnett
|
|
L, Tucker
|
|
K, Friedlander
|
|
M, Buckley
|
|
MF. The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data.
|
|
Cancer.
|
|
2001;92:440-5.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11466700" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11466700</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.basu.2015.531">Basu
|
|
NN, Ingham
|
|
S, Hodson
|
|
J, Lalloo
|
|
F, Bulman
|
|
M, Howell
|
|
A, Evans
|
|
DG. Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis.
|
|
Fam Cancer.
|
|
2015;14: 531-8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26239694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26239694</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.bernstein.2006.348">Bernstein
|
|
JL, Teraoka
|
|
SN, John
|
|
EM, Andrulis
|
|
IL, Knight
|
|
JA, Lapinski
|
|
R, Olson
|
|
ER, Wolitzer
|
|
AL, Seminara
|
|
D, Whittemore
|
|
AS, Concannon
|
|
P. The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the breast cancer family registry.
|
|
Cancer Epidemiol Biomarkers Prev.
|
|
2006;15:348-52
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16492927" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16492927</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.bolton.2012.382">Bolton
|
|
KL, Chenevix-Trench
|
|
G, Gob
|
|
C, Sadetzke
|
|
S, Ramus
|
|
SJ, Karlan
|
|
BY, Lambrechts
|
|
D, Despierre
|
|
E, Barrowdale
|
|
D, McGuffog
|
|
L, Healey
|
|
S, Easton
|
|
DF, Sinilnikova
|
|
O, Benetiz
|
|
J, Garcia
|
|
MJ, Neuhausen
|
|
S, Gail
|
|
MH, Hartge
|
|
P, Peock
|
|
S, Frost
|
|
D, Evans
|
|
DG, Eeles
|
|
R, Godwin
|
|
AK, Daly
|
|
MB, Kwong
|
|
A, Ma
|
|
EDK, Lazaro
|
|
C, Blanco
|
|
I, Montagna
|
|
M, D'Andrea
|
|
E, Nicoletto
|
|
MO, Johnatty
|
|
SF, Jjaer
|
|
SK, Jensen
|
|
A, Hogdall
|
|
E, Goode
|
|
EL, Fridley
|
|
BL, Loud
|
|
JT, Greene
|
|
MH, Mai
|
|
PL, Chetrit
|
|
A, Lubin
|
|
F, Hirsh-Yechezkel
|
|
G, Glendon
|
|
G, Andrulis
|
|
IL, Toland
|
|
AE, Senter
|
|
L, Gore
|
|
ME, Gourley
|
|
C, Michie
|
|
CO, Song
|
|
H, Tyrer
|
|
J, Whittemore
|
|
AS, McGuire
|
|
V, Sieh
|
|
W, Kristoffersson
|
|
U, Olsson
|
|
H, Borg
|
|
A, Levine
|
|
DA, Steele
|
|
L, Beattie
|
|
MS, Chan
|
|
S, Nussbaum
|
|
RL, Moysich
|
|
KB, Gross
|
|
J, Cass
|
|
I, Walsh
|
|
C, Li
|
|
AJ, Leuchter
|
|
R, Gordon
|
|
O, Garcia-Closas
|
|
M, Gayther
|
|
SA, Chanock
|
|
SJ, Antoniou
|
|
AC, Pharoah
|
|
PDP, et al.
|
|
Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer.
|
|
JAMA. 2012;307:382-90.
|
|
[<a href="/pmc/articles/PMC3727895/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3727895</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22274685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22274685</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.bordeleau.2010.13">Bordeleau
|
|
L, Panchal
|
|
S, Goodwin
|
|
P.
|
|
Prognosis of BRCA-associated breast cancer: a summary of evidence.
|
|
Breast Cancer Res Treat.
|
|
2010;119:13-24.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19789974" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19789974</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.bork.1997.68">Bork
|
|
P, Hofmann
|
|
K, Bucher
|
|
P, Neuwald
|
|
AF, Altschul
|
|
SF, Koonin
|
|
EV. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
|
|
FASEB J.
|
|
1997;11:68-76
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9034168" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9034168</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.breast_cancer_linkage_consortium.1999.1310">Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers.
|
|
J Natl Cancer Inst.
|
|
1999;91:1310-6
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10433620" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10433620</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.brose.2002.1365">Brose
|
|
MS, Rebbeck
|
|
TR, Calzone
|
|
KA, Stopfer
|
|
JE, Nathanson
|
|
KL, Weber
|
|
BL. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program.
|
|
J Natl Cancer Inst.
|
|
2002;94:1365-72.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12237282" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12237282</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.callebaut.1997.25">Callebaut
|
|
I, Mornon
|
|
JP. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.
|
|
FEBS Lett.
|
|
1997;400:25-30
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9000507" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9000507</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.casey.2005.457">Casey
|
|
MJ, Synder
|
|
C, Bewtra
|
|
C, Narod
|
|
SA, Watson
|
|
P, Lynch
|
|
HT. Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations.
|
|
Gynecol Oncol.
|
|
2005;97:457-67
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15863145" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15863145</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chek2_consortium.2004.1175">CHEK2 Consortium. CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies.
|
|
Am J Hum Genet.
|
|
2004;74:1175-82.
|
|
[<a href="/pmc/articles/PMC1182081/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1182081</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15122511" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15122511</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chen.2006.863">Chen
|
|
S, Iversen
|
|
ES, Friebel
|
|
T, Finkelstein
|
|
D, Weber
|
|
BL, Eisen
|
|
A, Peterson
|
|
LE, Schildkraut
|
|
JM, Isaacs
|
|
C, Peshkin
|
|
BN, Corio
|
|
C, Leondaridis
|
|
L, Tomlinson
|
|
G, Dutson
|
|
D, Kerber
|
|
R, Amos
|
|
CI, Strong
|
|
LC, Berry
|
|
DA, Euhus
|
|
DM, Parmigiani
|
|
G. Characterization of BRCA1 and BRCA2 mutations in a large United States sample.
|
|
J Clin Oncol.
|
|
2006;24:863-71.
|
|
[<a href="/pmc/articles/PMC2323978/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2323978</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16484695" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16484695</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chen.2007.1329">Chen
|
|
S, Parmigiani
|
|
G.
|
|
Meta-analysis of BRCA1 and BRCA2 penetrance.
|
|
J Clin Oncol.
|
|
2007;25:1329-33.
|
|
[<a href="/pmc/articles/PMC2267287/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2267287</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17416853" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17416853</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chen.1996.3168">Chen
|
|
Y, Farmer
|
|
AA, Chen
|
|
CF, Jones
|
|
DC, Chen
|
|
PL, Lee
|
|
WH. BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner.
|
|
Cancer Res.
|
|
1996;56:3168-72.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/8764100" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8764100</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chi.2021.17562848211014818">Chi
|
|
J, Chung
|
|
SY, Parakrama
|
|
R, Fayyaz
|
|
F, Jose
|
|
J, Saif
|
|
MW. The role of PARP inhibitors in BRCA mutated pancreatic cancer.
|
|
Therap Adv Gastroenterol.
|
|
2021;14:17562848211014818.
|
|
[<a href="/pmc/articles/PMC8120537/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8120537</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34025781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34025781</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.chlebowski.2003.3243">Chlebowski
|
|
RT, Hendrix
|
|
SL, Langer
|
|
RD, Stefanick
|
|
ML, Gass
|
|
M, Lane
|
|
D, Rodabough
|
|
RJ, Gilligan
|
|
MA, Cyr
|
|
MG, Thomson
|
|
CA, Khandekar
|
|
J, Petrovitch
|
|
H, McTiernan
|
|
A
|
|
Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.
|
|
JAMA. 2003; 289:3243-53
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12824205" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12824205</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.cibula.2011.55">Cibula
|
|
D, Widschwendter
|
|
M, Majek
|
|
O, Dusek
|
|
L. Tubal ligation and the risk of ovarian cancer: review and meta-analysis.
|
|
Hum Reprod Update.
|
|
2011;17:55-67.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20634209" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20634209</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.cousineau.2005.11384">Cousineau
|
|
I, Abaji
|
|
C, Belmaaza
|
|
A.
|
|
BRCA1 regulates RAD51 function in response to DNA damage and suppresses spontaneous sister chromatid replication slippage: implications for sister chromatid cohesion, genome stability, and carcinogenesis.
|
|
Cancer Res.
|
|
2005;65:11384-91
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16357146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16357146</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.cox.2018.1236">Cox
|
|
DM, Nelson
|
|
KL, Clytone
|
|
M, Collins
|
|
DL. Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations.
|
|
Mol Genet Genomic Med.
|
|
2018;6:1236-42.
|
|
[<a href="/pmc/articles/PMC6305650/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6305650</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30152102" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30152102</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.dagan.2008.267">Dagan
|
|
E.
|
|
Predominant Ashkenazi BRCA1/2 mutations in families with pancreatic cancer.
|
|
Genet Test.
|
|
2008;12:267-71.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18439109" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18439109</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.daly.2015.342">Daly
|
|
MB, Dresher
|
|
CW, Yates
|
|
MS, Jeter
|
|
JM, Karlan
|
|
BY, Alberts
|
|
DS, Lu
|
|
KH. Salpingectomy as a means to reduce ovarian cancer risk.
|
|
Cancer Prev Res (Phila). 2015;8:342-8.
|
|
[<a href="/pmc/articles/PMC4417454/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4417454</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25586903" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25586903</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.dann.2012.677">Dann
|
|
RB, DeLoia
|
|
JA, Timms
|
|
KM, Zorn
|
|
KK, Potter
|
|
J, Flake
|
|
DD, Lanchbury
|
|
JS, Kirvak
|
|
TC. BRCA1/2 muatations and expression: resonse to platinum chemogherapy in patients with advanced stage epithelial ovarian cancer.
|
|
Gynecol Oncol.
|
|
2012;125:677-82.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22406760" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22406760</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.de_bono.2020.2091">De Bono
|
|
J, Mateo
|
|
J, Fuzazi
|
|
K, Saad
|
|
F, Shore
|
|
N, Sandhu
|
|
S, Chi
|
|
KN, Sartor
|
|
O, Agarwal
|
|
N, Olmos
|
|
D, Thiery-Vuillemin
|
|
A, Twardowski
|
|
P, Mehra
|
|
N, Goessl
|
|
C, Kang
|
|
J, Burgents
|
|
J, Wu
|
|
W, Kohlmann
|
|
A, Adelman
|
|
CA, Hussain
|
|
M. Olaparib for metastatic castration-resistant prostate cancer.
|
|
N Engl J Med.
|
|
2020;382:2091-102.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32343890" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32343890</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.de_jonge.2017.215">de Jonge
|
|
MM, Mooyaart
|
|
AL, Vreeswijk
|
|
MP, de Kroon
|
|
CD, van Wezel
|
|
T, van Asperen
|
|
CJ, Smit
|
|
VT, Dekkers
|
|
OM, Bosse
|
|
T. Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: a meta-analysis and case report.
|
|
Eur J Cancer.
|
|
2017;72:215-25.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28049106" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28049106</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.de_la_hoya.2003.503">de la Hoya
|
|
M, Díez
|
|
O, Pérez-Segura
|
|
P, Godino
|
|
J, Fernández
|
|
JM, Sanz
|
|
J, Alonso
|
|
C, Baiget
|
|
M, Díaz-Rubio
|
|
E, Caldés
|
|
T. Pre-test prediction models of BRCA1 or BRCA2 mutation in breast/ovarian families attending familial cancer clinics.
|
|
J Med Genet.
|
|
2003;40:503-10.
|
|
[<a href="/pmc/articles/PMC1735524/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735524</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12843322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12843322</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.deng.2006.1416">Deng
|
|
CX. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution.
|
|
Nucleic Acids Research.
|
|
2006;34:1416-26
|
|
[<a href="/pmc/articles/PMC1390683/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1390683</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16522651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16522651</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.domchek.2011">Domchek SM, Friebel T, Neuhausen SL, Lynch HT, Singer CF, Eeles RA, Isaacs C, Tung NM, Ganz PA, Couch FJ, Weitzel JN, Olopade OI, Rubinstein WS, Tomlinson GE, Pichert GC, Daly MB, Matloff ET, Evans DG, Garber JE, Rebbeck TR, et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer. Abstract 1501. Chicago, IL: ASCO Annual Meeting; 2011.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.eisen.2008.1361">Eisen
|
|
A, Lubinski
|
|
J, Gronwald
|
|
J, Moller
|
|
P, Lynch
|
|
HT, Klijn
|
|
J, Kim-Sing
|
|
C, Neuhausen
|
|
SL, Gilbert
|
|
L, Ghadirian
|
|
P, Manoukian
|
|
S, Rennert
|
|
G, Friedman
|
|
E, Isaacs
|
|
C, Rosen
|
|
E, Rosen
|
|
B, Daly
|
|
M, Sun
|
|
P, Narod
|
|
SA, et al.
|
|
Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers.
|
|
J Natl Cancer Inst.
|
|
2008;100:1361-7.
|
|
[<a href="/pmc/articles/PMC2556701/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2556701</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18812548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18812548</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.euhus.2002.844">Euhus
|
|
DM, Smith
|
|
KC, Robinson
|
|
L, Stucky
|
|
A, Olopade
|
|
OI, Cummings
|
|
S, Garber
|
|
JE, Chittenden
|
|
A, Mills
|
|
GB, Rieger
|
|
P, Esserman
|
|
L, Crawford
|
|
B, Hughes
|
|
KS, Roche
|
|
CA, Ganz
|
|
PA, Seldon
|
|
J, Fabian
|
|
CJ, Klemp
|
|
J, Tomlinson
|
|
G. Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.
|
|
J Natl Cancer Inst.
|
|
2002;94:844-51.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12048272" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12048272</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.evans.2004.474">Evans
|
|
DG, Eccles
|
|
DM, Rahman
|
|
N, Young
|
|
K, Bulman
|
|
M, Amir
|
|
E, Shenton
|
|
A, Howell
|
|
A, Lalloo
|
|
F. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.
|
|
J Med Genet.
|
|
2004;41:474-80.
|
|
[<a href="/pmc/articles/PMC1735807/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735807</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15173236" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15173236</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.evans.2010.710">Evans
|
|
DG, Susnerwala
|
|
I, Dawson
|
|
J, Woodward
|
|
E, Maher
|
|
ER, Lalloo
|
|
F. Risk of breast cancer in male BRCA2 carriers.
|
|
J Med Genet.
|
|
2010;47:710-1.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20587410" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20587410</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.ferla.2007">Ferla R, Calò V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, Surmacz E, Colucci G, Bazan V, Russo A. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 18 Suppl. 2007;6:vi93-8. [<a href="https://pubmed.ncbi.nlm.nih.gov/17591843" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17591843</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.fong.2009.123">Fong
|
|
PC, Boss
|
|
DS, Yap
|
|
TA, Tutt
|
|
A, Wu
|
|
P, Mergui-Roelvink
|
|
M, Mortimer
|
|
P, Swaisland
|
|
H, Lau
|
|
A, O'Connor
|
|
MJ, Ashworth
|
|
A, Carmichael
|
|
J, Kaye
|
|
SB, Schellens
|
|
JH, de Bono
|
|
JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
|
|
N Engl J Med.
|
|
2009;361:123-34.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19553641" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19553641</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.frank.2002.1480">Frank
|
|
TS, Deffenbaugh
|
|
AM, Reid
|
|
JE, Hulick
|
|
M, Ward
|
|
BE, Lingenfelter
|
|
B, Gumpper
|
|
KL, Scholl
|
|
T, Tavtigian
|
|
SV, Pruss
|
|
DR, Critchfield
|
|
GC. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals.
|
|
J Clin Oncol.
|
|
2002;20:1480-90
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11896095" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11896095</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.friebel.2014.dju091">Friebel
|
|
TM, Domchek
|
|
SM, Rebbeck
|
|
TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis.
|
|
J Natl Cancer Inst.
|
|
2014;106:dju091.
|
|
[<a href="/pmc/articles/PMC4081625/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4081625</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24824314" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24824314</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.fujiwara.2012.1170">Fujiwara
|
|
M, McGuire
|
|
VA, Felberg
|
|
A, Sieh
|
|
W, Whittemore
|
|
AS, Longacre
|
|
TA. Prediction of BRCA1 germline mutation status in women with ovarian cancer using morphology-based criteria, identification of a BRCA1 ovarian cancer phenotype.
|
|
Am J Surg Pathol.
|
|
2012;36:1170-7.
|
|
[<a href="/pmc/articles/PMC3422129/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3422129</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22790858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22790858</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.gabaikapara.2014.14205">Gabai-Kapara
|
|
E, Lahad
|
|
A, Kaufman
|
|
B, Friedman
|
|
E, Segev
|
|
S, Renbaum
|
|
P, Beeri
|
|
R, Gal
|
|
M, Grinshpun-Cohen
|
|
J, Djemal
|
|
K, Mandell
|
|
JB, Lee
|
|
MK, Beller
|
|
U, Catane
|
|
R, King
|
|
MC, Levy-Lahad
|
|
E. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.
|
|
Proc Natl Acad Sci U S A.
|
|
2014;111:14205-10.
|
|
[<a href="/pmc/articles/PMC4191771/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4191771</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25192939" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25192939</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.gallagher.2010.2115">Gallagher
|
|
DJ, Gaudet
|
|
MM, Pal
|
|
P, Kirchhoff
|
|
T, Balistreri
|
|
L, Vora
|
|
K, Bhatia
|
|
J, Stadler
|
|
Z, Fine
|
|
SW, Reuter
|
|
V, Zelefsky
|
|
M, Morris
|
|
MJ, Scher
|
|
HI, Klein
|
|
RJ, Norton
|
|
L, Eastham
|
|
JA, Scardino
|
|
PT, Robson
|
|
ME, Offit
|
|
K. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer.
|
|
Clin Cancer Res.
|
|
2010;16:2115-21.
|
|
[<a href="/pmc/articles/PMC3713614/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3713614</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20215531" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20215531</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.golan.2014.1132">Golan
|
|
T, Kanji
|
|
ZS, Epelbaum
|
|
R, Devaud
|
|
N, Dagan
|
|
E, Holter
|
|
S, Aderka
|
|
D, Paluch-Shimon
|
|
S, Kaufman
|
|
B, Gershoni-Baruch
|
|
R, Hedley
|
|
D, Moore
|
|
MJ, Friedman
|
|
E, Gallinger
|
|
S. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.
|
|
Br J Cancer.
|
|
2014;111:1132-8.
|
|
[<a href="/pmc/articles/PMC4453851/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4453851</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25072261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25072261</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.golmard.2016.1324">Golmard
|
|
L, Delnatte
|
|
C, Laugé
|
|
A, Moncoutier
|
|
V, Lefol
|
|
C, Abidallah
|
|
K, Tenreiro
|
|
H, Copigny
|
|
F, Giraudeau
|
|
M, Guy
|
|
C, Barbaroux
|
|
C, Amorim
|
|
G, Briaux
|
|
A, Guibert
|
|
V, Tarabeux
|
|
J, Caputo
|
|
S, Collet
|
|
A, Gesta
|
|
P, Ingster
|
|
O, Stern
|
|
MH, Rouleau
|
|
E, de Pauw
|
|
A, Gauthier-Villars
|
|
M, Buecher
|
|
B, Bézieau
|
|
S, Stoppa-Lyonnet
|
|
D, Houdayer
|
|
C. Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations.
|
|
Oncogene.
|
|
2016;35:1324-7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26028024" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26028024</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.graeser.2009.5887">Graeser
|
|
MK, Engel
|
|
C, Rhiem
|
|
K, Gadzicki
|
|
D, Bick
|
|
U, Kast
|
|
K, Froster
|
|
UG, Schlehe
|
|
B, Bechtold
|
|
A, Arnold
|
|
N, Preisler-Adams
|
|
S, Nestle-Kraemling
|
|
C, Zaino
|
|
M, Loeffler
|
|
M, Kiechle
|
|
M, Meindl
|
|
A, Varga
|
|
D, Schmutzler
|
|
RK. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.
|
|
J Clin Oncol.
|
|
2009;27:5887-92.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19858402" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19858402</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.gronwald.2006.2281">Gronwald
|
|
J, Tung
|
|
N, Foulkes
|
|
WD, Offit
|
|
K, Gershoni
|
|
R, Daly
|
|
M, Kim-Sing
|
|
C, Olsson
|
|
H, Ainsworth
|
|
P, Eisen
|
|
A, Saal
|
|
H, Friedman
|
|
E, Olopade
|
|
O, Osborne
|
|
M, Weitzel
|
|
J, Lynch
|
|
H, Ghadirian
|
|
P, Lubinski
|
|
J, Sun
|
|
P, Narod
|
|
SA, et al.
|
|
Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update.
|
|
Int J Cancer.
|
|
2006;118:2281-4.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16331614" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16331614</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.gumaste.2015.1498">Gumaste
|
|
PV, Penn
|
|
LA, Cymerman
|
|
RM, Kirchhoff
|
|
T, Polsky
|
|
D, McLellan
|
|
B. Skin cancer risk in BRCA1/2 mutation carriers.
|
|
Br J Dermatol.
|
|
2015;172:1498-506.
|
|
[<a href="/pmc/articles/PMC5785081/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5785081</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25524463" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25524463</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.haffty.2002.1471">Haffty
|
|
BG, Harrold
|
|
E, Khan
|
|
AJ, Pathare
|
|
P, Smith
|
|
TE, Turner
|
|
BC, Glazer
|
|
PM, Ward
|
|
B, Carter
|
|
D, Matloff
|
|
E, Bale
|
|
AE, Alvarez-Franco
|
|
M. Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status.
|
|
Lancet.
|
|
2002;359:1471-7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11988246" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11988246</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.hansen.2009.69">Hansen
|
|
TV, Ejlertsen
|
|
B, Albrechtsen
|
|
A, Bergsten
|
|
E, Bjerregaard
|
|
P, Hansen
|
|
T, Myrhøj
|
|
T, Nielsen
|
|
PB, Timmermans-Wielenga
|
|
V, Andersen
|
|
MK, Jønson
|
|
L, Nielsen
|
|
FC. A common Greenlandic Inuit BRCA1 RING domain founder mutation.
|
|
Breast Cancer Res Treat.
|
|
2009;115:69-76.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18500671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18500671</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.hansen.2010.259">Hansen
|
|
TV, Jønson
|
|
L, Albrechtsen
|
|
A, Steffensen
|
|
AY, Bergsten
|
|
E, Myrhøj
|
|
T, Ejlertsen
|
|
B, Nielsen
|
|
FC. Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer.
|
|
Breast Cancer Res Treat.
|
|
2010;124:259-64.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20437199" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20437199</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.harboe.2009.413">Harboe
|
|
TL, Eiberg
|
|
H, Kern
|
|
P, Ejlertsen
|
|
B, Nedergaard
|
|
L, Timmermans-Wielenga
|
|
V, Nielsen
|
|
IM, Bisgaard
|
|
ML. A high frequent BRCA1 founder mutation identified in the Greenlandic population.
|
|
Fam Cancer.
|
|
2009;8:413-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19504351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19504351</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.hearle.2003.458">Hearle
|
|
N, Damato
|
|
BE, Humphreys
|
|
J, Wixey
|
|
J, Green
|
|
H, Stone
|
|
J, Easton
|
|
DF, Houlston
|
|
RS. Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma.
|
|
Invest Ophthalmol Vis Sci.
|
|
2003;44:458-62.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12556369" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12556369</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.ibrahim.2018.179">Ibrahim
|
|
M, Yadav
|
|
S, Ogunleye
|
|
F, Zakalik
|
|
D.
|
|
Male BRCA mutation carriers: clinical characteristics and cancer spectrum.
|
|
BMC Cancer.
|
|
2018;18:179.
|
|
[<a href="/pmc/articles/PMC5809938/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5809938</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29433453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29433453</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.iodice.2010.2275">Iodice
|
|
S, Barile
|
|
M, Rotmensz
|
|
N, Feroce
|
|
I, Bonanni
|
|
B, Radice
|
|
P, Bernard
|
|
L, Maisonneuve
|
|
P, Gandini
|
|
S. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis.
|
|
Eur J Cancer.
|
|
2010;46: 2275-84.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20537530" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20537530</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.iqbal.2012.2005">Iqbal
|
|
J, Ragone
|
|
A, Lubinski
|
|
J, Lynch
|
|
HT, Moller
|
|
P, Ghadirian
|
|
P, Foulkes
|
|
WD, Armel
|
|
S, Eisen
|
|
A, Neuhausen
|
|
SL, Senter
|
|
L, Singer
|
|
CF, Ainsworth
|
|
P, Kim-Sing
|
|
C, Tung
|
|
N, Friedman
|
|
E, Llacuachaqui
|
|
M, Ping
|
|
S, Narod
|
|
SA, et al.
|
|
The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers.
|
|
Br J Cancer.
|
|
2012;107:2005-9.
|
|
[<a href="/pmc/articles/PMC3516682/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3516682</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23099806" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23099806</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.jeong.2021.3509">Jeong
|
|
KY, Park
|
|
MH. The significance of targeting poly (ADP-ribose) polymerase-1 in pancreatic cancer for providing a new therapeutic paradigm.
|
|
Int J Mol Sci.
|
|
2021;22:3509-24.
|
|
[<a href="/pmc/articles/PMC8037971/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8037971</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33805293" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33805293</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.jernstr_m.2004.1094">Jernström
|
|
H, Lubinski
|
|
J, Lynch
|
|
HT, Ghadirian
|
|
P, Neuhausen
|
|
S, Isaacs
|
|
C, Weber
|
|
BL, Horsman
|
|
D, Rosen
|
|
B, Foulkes
|
|
WD, Friedman
|
|
E, Gershoni-Baruch
|
|
R, Ainsworth
|
|
P, Daly
|
|
M, Garber
|
|
J, Olsson
|
|
H, Sun
|
|
P, Narod
|
|
SA. Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
|
|
J Natl Cancer Inst.
|
|
2004;96:1094-8
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15265971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15265971</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kaufman.2015.244">Kaufman
|
|
B, Shapira-Frommer
|
|
R, Schmutzler
|
|
RK, Audeh
|
|
MW, Friedlander
|
|
M, Balmaña
|
|
J, Mitchell
|
|
G, Fried
|
|
G, Stemmer
|
|
SM, Hubert
|
|
A, Rosengarten
|
|
O, Steiner
|
|
M, Loman
|
|
N, Bowen
|
|
K, Fielding
|
|
A, Domchek
|
|
SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.
|
|
J Clin Oncol.
|
|
2015;33:244-50.
|
|
[<a href="/pmc/articles/PMC6057749/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6057749</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25366685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25366685</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.king.2001.2251">King
|
|
MC, Wieand
|
|
S, Hale
|
|
K, Lee
|
|
M, Walsh
|
|
T, Owens
|
|
K, Tait
|
|
J, Ford
|
|
L, Dunn
|
|
BK, Costantino
|
|
J, Wickerham
|
|
L, Wolmark
|
|
N, Fisher
|
|
B, et al.
|
|
Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial.
|
|
JAMA. 2001;286:2251-6
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11710890" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11710890</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kirova.2005.2304">Kirova
|
|
YM, Stoppa-Lyonnet
|
|
D, Savignoni
|
|
A, Sigal-Zafrani
|
|
B, Fabre
|
|
N, Fourquet
|
|
A, et al.
|
|
Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy.
|
|
Eur J Cancer.
|
|
2005;41:2304-11.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16140006" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16140006</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kotejarai.2011.1230">Kote-Jarai
|
|
Z, Leongamornlert
|
|
D, Saunders
|
|
E, Tymrakiewicz
|
|
M, Castro
|
|
E, Mahmud
|
|
N, Guy
|
|
M, Edwards
|
|
S, O'Brien
|
|
L, Sawyer
|
|
E, Hall
|
|
A, Wilkinson
|
|
R, Dadaev
|
|
T, Goh
|
|
C, Easton
|
|
D; UKGPCS
|
|
Collaborators, Goldgar
|
|
D, Eeles
|
|
R. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.
|
|
Br J Cancer.
|
|
2011;105:1230-4.
|
|
[<a href="/pmc/articles/PMC3208504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3208504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21952622" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21952622</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kotsopoulos.2016.365">Kotsopoulos
|
|
J, Huzarski
|
|
T, Gronwald
|
|
J, Moller
|
|
P, Lynch
|
|
HT, Neuhausen
|
|
SL, Senter
|
|
L, Demsky
|
|
R, Foulkes
|
|
WD, Eng
|
|
C, Karlan
|
|
B, Tung
|
|
N, Singer
|
|
CF, Sun
|
|
P, Lubinski
|
|
J, Narod
|
|
SA. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study.
|
|
Breast Cancer Res Treat.
|
|
2016;155:365-73.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26780555" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26780555</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kotsopoulos.2015.1136">Kotsopoulos
|
|
J, Lubinski
|
|
J, Gronwald
|
|
J, Cybulski
|
|
C, Demsky
|
|
R, Neuhausen
|
|
SL, Kim-Sing
|
|
C, Tung
|
|
N, Friedman
|
|
S, Senter
|
|
L, Weitzel
|
|
J, Karlan
|
|
B, Moller
|
|
P, Sun
|
|
P, Narod
|
|
SA, et al.
|
|
Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
|
|
Int J Cancer.
|
|
2015;137:1136-46.
|
|
[<a href="/pmc/articles/PMC4458227/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4458227</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25482078" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25482078</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kowalewski.2018.1503">Kowalewski
|
|
A, Szylberg
|
|
Ł, Saganek
|
|
M, Napiontek
|
|
W, Antosik
|
|
P, Grzanka
|
|
D.
|
|
Emerging strategies in BRCA-positive pancreatic cancer.
|
|
J Cancer Res Clin Oncol.
|
|
2018;144:1503-7.
|
|
[<a href="/pmc/articles/PMC6061050/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6061050</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29777302" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29777302</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.kuchenbaecker.2017.2402">Kuchenbaecker
|
|
KB, Hopper
|
|
JL, Barnes
|
|
DR, Phillips
|
|
KA, Mooij
|
|
TM, Roos-Blom
|
|
MJ, Jervis
|
|
S, van Leeuwen
|
|
FE, Milne
|
|
RL, Andrieu
|
|
N, Goldgar
|
|
DE, Terry
|
|
MB, Rookus
|
|
MA, Easton
|
|
DF, Antoniou
|
|
AC, McGuffog
|
|
L, Evans
|
|
DG, Barrowdale
|
|
D, Frost
|
|
D, Adlard
|
|
J, Ong
|
|
KR, Izatt
|
|
L, Tischkowitz
|
|
M, Eeles
|
|
R, Davidson
|
|
R, Hodgson
|
|
S, Ellis
|
|
S, Nogues
|
|
C, Lasset
|
|
C, Stoppa-Lyonnet
|
|
D, Fricker
|
|
JP, Faivre
|
|
L, Berthet
|
|
P, Hooning
|
|
MJ, van der Kolk
|
|
LE, Kets
|
|
CM, Adank
|
|
MA, John
|
|
EM, Chung
|
|
WK, Andrulis
|
|
IL, Southey
|
|
M, Daly
|
|
MB, Buys
|
|
SS, Osorio
|
|
A, Engel
|
|
C, Kast
|
|
K, Schmutzler
|
|
RK, Caldes
|
|
T, Jakubowska
|
|
A, Simard
|
|
J, Friedlander
|
|
ML, McLachlan
|
|
SA, Machackova
|
|
E, Foretova
|
|
L, Tan
|
|
YY, Singer
|
|
CF, Olah
|
|
E, Gerdes
|
|
AM, Arver
|
|
B, Olsson
|
|
H, et al.
|
|
Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
|
|
JAMA. 2017;317:2402-16.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28632866" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28632866</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.laduca.2020.407">LaDuca
|
|
H, Polley
|
|
EC, Yussuf
|
|
A, Hoang
|
|
L, Gutierrez
|
|
S, Hart
|
|
SN, Yadav
|
|
S, Hu
|
|
C, Na
|
|
J, Goldgar
|
|
DE, Fulk
|
|
K, Smith
|
|
LP, Horton
|
|
C, Profato
|
|
J, Pesaran
|
|
T, Gau
|
|
CL, Pronold
|
|
M, Davis
|
|
BT, Chao
|
|
EC, Couch
|
|
FJ, Dolinsky
|
|
JS. A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients.
|
|
Genet Med.
|
|
2020;22:407-15.
|
|
[<a href="/pmc/articles/PMC7000322/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7000322</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31406321" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31406321</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.ledermann.2014.852">Ledermann
|
|
J, Harter
|
|
P, Gourley
|
|
C, Friedlander
|
|
M, Vergote
|
|
I, Rustin
|
|
G, Scott
|
|
CL, Meier
|
|
W, Shapira-Frommer
|
|
R, Safra
|
|
T, Matei
|
|
D, Fielding
|
|
A, Spencer
|
|
S, Dougherty
|
|
B, Orr
|
|
M, Hodgson
|
|
D, Barrett
|
|
JC, Matulonis
|
|
U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.
|
|
Lancet Oncol.
|
|
2014;15:852-61.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24882434" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24882434</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.lee.2011.4373">Lee
|
|
E, McKean-Cowdin
|
|
R, Ma
|
|
H, Spicer
|
|
DV, Van Den Berg
|
|
D, Bernstein
|
|
L, Ursin
|
|
G. Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation: results from a population-based study of young women.
|
|
J Clin Oncol.
|
|
2011;29:4373-80.
|
|
[<a href="/pmc/articles/PMC3221522/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3221522</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22010008" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22010008</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.leongamornlert.2012.1697">Leongamornlert
|
|
D, Mahmud
|
|
N, Tymrakiewicz
|
|
M, Saunders
|
|
E, Dadaev
|
|
T, Castro
|
|
E, Goh
|
|
C, Govindasami
|
|
K, Guy
|
|
M, O'Brien
|
|
L, Sawyer
|
|
E, Hall
|
|
A, Wilkinson
|
|
R, Easton
|
|
D, Goldgar
|
|
D, Eeles
|
|
R, Kote-Jarai
|
|
Z, et al.
|
|
Germline BRCA1 mutations increase prostate cancer risk.
|
|
Br J Cancer.
|
|
2012;106:1697-701.
|
|
[<a href="/pmc/articles/PMC3349179/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3349179</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22516946" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22516946</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.litton.2018.753">Litton
|
|
JK, Rugo
|
|
HS, Ettl
|
|
J, Hurvitz
|
|
SA, Gonçalves
|
|
A, Lee
|
|
KH, Fehrenbacher
|
|
L, Yerushalmi
|
|
R, Mina
|
|
LA, Martin
|
|
M, Roché
|
|
H, Im
|
|
YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation.
|
|
N Engl J Med.
|
|
2018;379:753-63.
|
|
[<a href="/pmc/articles/PMC10600918/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10600918</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30110579" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30110579</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.liu.2012.34">Liu
|
|
J, Cristea
|
|
MC, Frankel
|
|
P, Neuhausen
|
|
SL, Steele
|
|
L, Engelstaedter
|
|
V, Matulonis
|
|
U, Sand
|
|
S, Tung
|
|
N, Garber
|
|
JE, Weitzel
|
|
JN. Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival.
|
|
Cancer Genet.
|
|
2012;205: 34-41.
|
|
[<a href="/pmc/articles/PMC3337330/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3337330</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22429596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22429596</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.macchini.2021.102262">Macchini
|
|
M, Centonze
|
|
F, Peretti
|
|
U, Orsi
|
|
G, Militello
|
|
AM, Valente
|
|
MM, Cascinu
|
|
S, Reni
|
|
M. Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants.
|
|
Cancer Treat Rev.
|
|
2021;100:102262.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/34418781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34418781</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.malone.2010.2404">Malone
|
|
KE, Begg
|
|
CB, Haile
|
|
RW, Borg
|
|
A, Concannon
|
|
P, Tellhed
|
|
L, Xue
|
|
S, Teraoka
|
|
S, Bernstein
|
|
L, Capanu
|
|
M, Reiner
|
|
AS, Riedel
|
|
ER, Thomas
|
|
DC, Mellemkjaer
|
|
L, Lynch
|
|
C, Boice
|
|
JD, Anton-Culver
|
|
H, Bernstein
|
|
JL. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2.
|
|
J Clin Oncol.
|
|
2010;28:2404-10.
|
|
[<a href="/pmc/articles/PMC2881721/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2881721</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20368571" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20368571</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.marchetti.2014.150">Marchetti
|
|
C, De Felice
|
|
F, Palaia
|
|
I, Perniola
|
|
G, Musella
|
|
A, Musio
|
|
D, Muzii
|
|
L, Tombolini
|
|
V, Panici
|
|
PB. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers.
|
|
BMC Womens Health.
|
|
2014;14:150.
|
|
[<a href="/pmc/articles/PMC4271468/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4271468</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25494812" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25494812</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.mavaddat.2012.134">Mavaddat
|
|
N, Barrowdale
|
|
D, Andrulis
|
|
IL, Domchek
|
|
SM, Eccles
|
|
D, Nevanlinna
|
|
H, Ramus
|
|
SJ, Spurdle
|
|
A, Robson
|
|
M, Sherman
|
|
M, Mulligan
|
|
AM, Couch
|
|
FJ, Engel
|
|
C, McGuffog
|
|
L, Healey
|
|
S, Sinilnikova
|
|
OM, Southey
|
|
MC, Terry
|
|
MB, Goldgar
|
|
D, O'Malley
|
|
F, John
|
|
EM, Janavicius
|
|
R, Tihomirova
|
|
L, Hansen
|
|
TV, Nielsen
|
|
FC, Osorio
|
|
A, Stavropoulou
|
|
A, Benítez
|
|
J, Manoukian
|
|
S, Peissel
|
|
B, Barile
|
|
M, Volorio
|
|
S, Pasini
|
|
B, Dolcetti
|
|
R, Putignano
|
|
AL, Ottini
|
|
L, Radice
|
|
P, Hamann
|
|
U, Rashid
|
|
MU, Hogervorst
|
|
FB, Kriege
|
|
M, van der Luijt
|
|
RB, Peock
|
|
S, Frost
|
|
D, Evans
|
|
DG, Brewer
|
|
C, Walker
|
|
L, Rogers
|
|
MT, Side
|
|
LE, Houghton
|
|
C, Weaver
|
|
J, Godwin
|
|
AK, Schmutzler
|
|
RK, Wappenschmidt
|
|
B, Meindl
|
|
A, Kast
|
|
K, Arnold
|
|
N, Niederacher
|
|
D, Sutter
|
|
C, Deissler
|
|
H, Gadzicki
|
|
D, Preisler-Adams
|
|
S, Varon-Mateeva
|
|
R, Schönbuchner
|
|
I, Gevensleben
|
|
H, Stoppa-Lyonnet
|
|
D, Belotti
|
|
M, Barjhoux
|
|
L, Isaacs
|
|
C, Peshkin
|
|
BN, Caldes
|
|
T, de la Hoya
|
|
M, Cañadas
|
|
C, Heikkinen
|
|
T, Heikkilä
|
|
P, Aittomäki
|
|
K, Blanco
|
|
I, Lazaro
|
|
C, Brunet
|
|
J, Agnarsson
|
|
BA, Arason
|
|
A, Barkardottir
|
|
RB, Dumont
|
|
M, Simard
|
|
J, Montagna
|
|
M, Agata
|
|
S, D'Andrea
|
|
E, Yan
|
|
M, Fox
|
|
S, Rebbeck
|
|
TR, Rubinstein
|
|
W, Tung
|
|
N, Garber
|
|
JE, Wang
|
|
X, Fredericksen
|
|
Z, Pankratz
|
|
VS, Lindor
|
|
NM, Szabo
|
|
C, Offit
|
|
K, Sakr
|
|
R, Gaudet
|
|
MM, Singer
|
|
CF, Tea
|
|
MK, Rappaport
|
|
C, Mai
|
|
PL, Greene
|
|
MH, Sokolenko
|
|
A, Imyanitov
|
|
E, Toland
|
|
AE, Senter
|
|
L, Sweet
|
|
K, Thomassen
|
|
M, Gerdes
|
|
AM, Kruse
|
|
T, Caligo
|
|
M, Aretini
|
|
P, Rantala
|
|
J, von Wachenfeld
|
|
A, Henriksson
|
|
K, Steele
|
|
L, Neuhausen
|
|
SL, Nussbaum
|
|
R, Beattie
|
|
M, Odunsi
|
|
K, Sucheston
|
|
L, Gayther
|
|
SA, Nathanson
|
|
K, Gross
|
|
J, Walsh
|
|
C, Karlan
|
|
B, Chenevix-Trench
|
|
G, Easton
|
|
DF, Antoniou
|
|
AC, et al.
|
|
Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
|
|
Cancer Epidemiol Biomarkers Prev.
|
|
2012;21:134-47.
|
|
[<a href="/pmc/articles/PMC3272407/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3272407</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22144499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22144499</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.mavaddat.2013.812">Mavaddat
|
|
N, Peock
|
|
S, Frost
|
|
D, Ellis
|
|
S, Platte
|
|
R, Fineberg
|
|
E, Evans
|
|
DG, Izatt
|
|
L, Eeles
|
|
RA, Adlard
|
|
J, Davidson
|
|
R, Eccles
|
|
D, Cole
|
|
T, Cook
|
|
J, Brewer
|
|
C, Tischkowitz
|
|
M, Douglas
|
|
F, Hodgson
|
|
S, Walker
|
|
L, Porteous
|
|
ME, Morrison
|
|
PJ, Side
|
|
LE, Kennedy
|
|
MJ, Houghton
|
|
C, Donaldson
|
|
A, Rogers
|
|
MT, Dorkins
|
|
H, Miedzybrodzka
|
|
Z, Gregory
|
|
H, Eason
|
|
J, Barwell
|
|
J, McCann
|
|
E, Murray
|
|
A, Antoniou
|
|
AC, Easton
|
|
DF, et al.
|
|
Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.
|
|
J Natl Cancer Inst.
|
|
2013;105:812-22.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23628597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23628597</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.mclaughlin.2013.141">McLaughlin
|
|
JR, Rosen
|
|
B, Moody
|
|
J, Pal
|
|
T, Fan
|
|
I, Shaw
|
|
PA, Risch
|
|
HA, Sellers
|
|
TA, Sun
|
|
P, Narod
|
|
SA. Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2.
|
|
J Natl Cancer Inst.
|
|
2013;105:141-8.
|
|
[<a href="/pmc/articles/PMC3611851/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3611851</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23257159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23257159</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.meeks.2015.djv315">Meeks
|
|
HD, Song
|
|
H, Michailidou
|
|
K, Bolla
|
|
MK, Dennis
|
|
J, Wang
|
|
Q, Barrowdale
|
|
D, Frost
|
|
D, McGuffog
|
|
L, Ellis
|
|
S, Feng
|
|
B, Buys
|
|
SS, Hopper
|
|
JL, Southey
|
|
MC, Tesoriero
|
|
A, James
|
|
PA, Bruinsma
|
|
F, Campbell
|
|
IG, Broeks
|
|
A, Schmidt
|
|
MK, Hogervorst
|
|
FB, Beckman
|
|
MW, Fasching
|
|
PA, Fletcher
|
|
O, Johnson
|
|
N, Sawyer
|
|
EJ, Riboli
|
|
E, Banerjee
|
|
S, Menon
|
|
U, Tomlinson
|
|
I, Burwinkel
|
|
B, Hamann
|
|
U, Marme
|
|
F, Rudolph
|
|
A, Janavicius
|
|
R, Tihomirova
|
|
L, Tung
|
|
N, Garber
|
|
J, Cramer
|
|
D, Terry
|
|
KL, Poole
|
|
EM, Tworoger
|
|
SS, Dorfling
|
|
CM, van Rensburg
|
|
EJ, Godwin
|
|
AK, Guénel
|
|
P, Truong
|
|
T, Stoppa-Lyonnet
|
|
D, Damiola
|
|
F, Mazoyer
|
|
S, Sinilnikova
|
|
OM, Isaacs
|
|
C, Maugard
|
|
C, Bojesen
|
|
SE, Flyger
|
|
H, Gerdes
|
|
AM, Hansen
|
|
TV, Jensen
|
|
A, Kjaer
|
|
SK, Hogdall
|
|
C, Hogdall
|
|
E, Pedersen
|
|
IS, Thomassen
|
|
M, Benitez
|
|
J, González-Neira
|
|
A, Osorio
|
|
A, Hoya Mde
|
|
L, Segura
|
|
PP, Diez
|
|
O, Lazaro
|
|
C, Brunet
|
|
J, Anton-Culver
|
|
H, Eunjung
|
|
L, John
|
|
EM, Neuhausen
|
|
SL, Ding
|
|
YC, Castillo
|
|
D, Weitzel
|
|
JN, Ganz
|
|
PA, Nussbaum
|
|
RL, Chan
|
|
SB, Karlan
|
|
BY, Lester
|
|
J, Wu
|
|
A, Gayther
|
|
S, Ramus
|
|
SJ, Sieh
|
|
W, Whittermore
|
|
AS, Monteiro
|
|
AN, Phelan
|
|
CM, Terry
|
|
MB, Piedmonte
|
|
M, Offit
|
|
K, Robson
|
|
M, Levine
|
|
D, Moysich
|
|
KB, Cannioto
|
|
R, Olson
|
|
SH, Daly
|
|
MB, Nathanson
|
|
KL, Domchek
|
|
SM, Lu
|
|
KH, Liang
|
|
D, Hildebrant
|
|
MA, Ness
|
|
R, Modugno
|
|
F, Pearce
|
|
L, Goodman
|
|
MT, Thompson
|
|
PJ, Brenner
|
|
H, Butterbach
|
|
K, Meindl
|
|
A, Hahnen
|
|
E, Wappenschmidt
|
|
B, Brauch
|
|
H, Brüning
|
|
T, Blomqvist
|
|
C, Khan
|
|
S, Nevanlinna
|
|
H, Pelttari
|
|
LM, Aittomäki
|
|
K, Butzow
|
|
R, Bogdanova
|
|
NV, Dörk
|
|
T, Lindblom
|
|
A, Margolin
|
|
S, Rantala
|
|
J, Kosma
|
|
VM, Mannermaa
|
|
A, Lambrechts
|
|
D, Neven
|
|
P, Claes
|
|
KB, Maerken
|
|
TV, Chang-Claude
|
|
J, Flesch-Janys
|
|
D, Heitz
|
|
F, Varon-Mateeva
|
|
R, Peterlongo
|
|
P, Radice
|
|
P, Viel
|
|
A, Barile
|
|
M, Peissel
|
|
B, Manoukian
|
|
S, Montagna
|
|
M, Oliani
|
|
C, Peixoto
|
|
A, Teixeira
|
|
MR, Collavoli
|
|
A, Hallberg
|
|
E, Olson
|
|
JE, Goode
|
|
EL, Hart
|
|
SN, Shimelis
|
|
H, Cunningham
|
|
JM, Giles
|
|
GG, Milne
|
|
RL, Healey
|
|
S, Tucker
|
|
K, Haiman
|
|
CA, Henderson
|
|
BE, Goldberg
|
|
MS, Tischkowitz
|
|
M, Simard
|
|
J, Soucy
|
|
P, Eccles
|
|
DM, Le
|
|
N, Borresen-Dale
|
|
AL, Kristensen
|
|
V, Salvesen
|
|
HB, Bjorge
|
|
L, Bandera
|
|
EV, Risch
|
|
H, Zheng
|
|
W, Beeghly-Fadiel
|
|
A, Cai
|
|
H, Pylkäs
|
|
K, Tollenaar
|
|
RA, Ouweland
|
|
AM, Andrulis
|
|
IL, Knight
|
|
JA, Narod
|
|
S, Devilee
|
|
P, Winqvist
|
|
R, Figueroa
|
|
J, Greene
|
|
MH, Mai
|
|
PL, Loud
|
|
JT, García-Closas
|
|
M, Schoemaker
|
|
MJ, Czene
|
|
K, Darabi
|
|
H, McNeish
|
|
I, Siddiquil
|
|
N, Glasspool
|
|
R, Kwong
|
|
A, Park
|
|
SK, Teo
|
|
SH, Yoon
|
|
SY, Matsuo
|
|
K, Hosono
|
|
S, Woo
|
|
YL, Gao
|
|
YT, Foretova
|
|
L, Singer
|
|
CF, Rappaport-Feurhauser
|
|
C, Friedman
|
|
E, Laitman
|
|
Y, Rennert
|
|
G, Imyanitov
|
|
EN, Hulick
|
|
PJ, Olopade
|
|
OI, Senter
|
|
L, Olah
|
|
E, Doherty
|
|
JA, Schildkraut
|
|
J, Koppert
|
|
LB, Kiemeney
|
|
LA, Massuger
|
|
LF, Cook
|
|
LS, Pejovic
|
|
T, Li
|
|
J, Borg
|
|
A, Öfverholm
|
|
A, Rossing
|
|
MA, Wentzensen
|
|
N, Henriksson
|
|
K, Cox
|
|
A, Cross
|
|
SS, Pasini
|
|
BJ, Shah
|
|
M, Kabisch
|
|
M, Torres
|
|
D, Jakubowska
|
|
A, Lubinski
|
|
J, Gronwald
|
|
J, Agnarsson
|
|
BA, Kupryjanczyk
|
|
J, Moes-Sosnowska
|
|
J, Fostira
|
|
F, Konstantopoulou
|
|
I, Slager
|
|
S, Jones
|
|
M, Antoniou
|
|
AC, Berchuck
|
|
A, Swerdlow
|
|
A, Chenevix-Trench
|
|
G, Dunning
|
|
AM, Pharoah
|
|
PD, Hall
|
|
P, Easton
|
|
DF, Couch
|
|
FJ, Spurdle
|
|
AB, Goldgar
|
|
DE, et al.
|
|
BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers.
|
|
J Natl Cancer Inst.
|
|
2015;108: djv315.
|
|
[<a href="/pmc/articles/PMC4907358/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4907358</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26586665" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26586665</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.mefford.1999.575">Mefford
|
|
HC, Baumbach
|
|
L, Panguluri
|
|
RC, Whitfield-Broome
|
|
C, Szabo
|
|
C, Smith
|
|
S, King
|
|
MC, Dunston
|
|
G, Stoppa-Lyonnet
|
|
D, Arena
|
|
F. Evidence for a BRCA1 founder mutation in families of West African ancestry.
|
|
Am J Hum Genet.
|
|
1999;65:575-8.
|
|
[<a href="/pmc/articles/PMC1377959/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1377959</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10417303" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10417303</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.mersch.2015.269">Mersch
|
|
J, Jackson
|
|
MA, Park
|
|
M, Nebgen
|
|
D, Peterson
|
|
SK, Singletary
|
|
C, Arun
|
|
BK, Litton
|
|
JK. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian.
|
|
Cancer.
|
|
2015;121:269-75.
|
|
[<a href="/pmc/articles/PMC4293332/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4293332</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25224030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25224030</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.metcalfe.2011a.1384">Metcalfe
|
|
K, Gershman
|
|
S, Lynch
|
|
HT, Ghadirian
|
|
P, Tung
|
|
N, Kim-Sing
|
|
C, Olopade
|
|
OI, Domchek
|
|
S, McLennan
|
|
J, Eisen
|
|
A, Foulkes
|
|
WD, Rosen
|
|
B, Sun
|
|
P, Narod
|
|
SA. Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.
|
|
Br J Cancer.
|
|
2011a;104:1384-92.
|
|
[<a href="/pmc/articles/PMC3101934/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3101934</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21487411" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21487411</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.metcalfe.2011b.287">Metcalfe
|
|
K, Lynch
|
|
HT, Ghadirian
|
|
P, Tung
|
|
N, Kim-Sing
|
|
C, Olopade
|
|
OI, Domchek
|
|
S, Eisen
|
|
A, Foulkes
|
|
WD, Rosen
|
|
B, Vesprini
|
|
D, Sun
|
|
P, Narod
|
|
SA. Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers.
|
|
Breast Cancer Res Treat.
|
|
2011b;127:287-96
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21221768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21221768</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.moghadasi.2018.15">Moghadasi
|
|
S, Meeks
|
|
HD, Vreeswijk
|
|
MP, Janssen
|
|
LA, Borg
|
|
Å, Ehrencrona
|
|
H, Paulsson-Karlsson
|
|
Y, Wappenschmidt
|
|
B, Engel
|
|
C, Gehrig
|
|
A, Arnold
|
|
N, Hansen
|
|
TVO, Thomassen
|
|
M, Jensen
|
|
UB, Kruse
|
|
TA, Ejlertsen
|
|
B, Gerdes
|
|
AM, Pedersen
|
|
IS, Caputo
|
|
SM, Couch
|
|
F, Hallberg
|
|
EJ, van den Ouweland
|
|
AM, Collée
|
|
MJ, Teugels
|
|
E, Adank
|
|
MA, van der Luijt
|
|
RB, Mensenkamp
|
|
AR, Oosterwijk
|
|
JC, Blok
|
|
MJ, Janin
|
|
N, Claes
|
|
KB, Tucker
|
|
K, Viassolo
|
|
V, Toland
|
|
AE, Eccles
|
|
DE, Devilee
|
|
P, Van Asperen
|
|
CJ, Spurdle
|
|
AB, Goldgar
|
|
DE, García
|
|
EG. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium.
|
|
J Med Genet.
|
|
2018;55:15-20.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28490613" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28490613</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.molinamontes.2014.721">Molina-Montes
|
|
E, Pérez-Nevot
|
|
B, Pollán
|
|
M, Sánchez-Cantalejo
|
|
E, Espín
|
|
J, Sánchez
|
|
MJ. Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: a systematic review and meta-analysis.
|
|
Breast.
|
|
2014;23:721-42.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25467311" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25467311</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.moore.2018.2495">Moore
|
|
K, Colombo
|
|
N, Scambia
|
|
G, Kim
|
|
BG, Oaknin
|
|
A, Friedlander
|
|
M, Lisyanskaya
|
|
A, Floquet
|
|
A, Leary
|
|
A, Sonke
|
|
GS, Gourley
|
|
C, Banerjee
|
|
S, Oza
|
|
A, González-Martín
|
|
A, Aghajanian
|
|
C, Bradley
|
|
W, Mathews
|
|
C, Liu
|
|
J, Lowe
|
|
ES, Bloomfield
|
|
R, DiSilvestro
|
|
P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer.
|
|
N Engl J Med.
|
|
2018;379:2495-505.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30345884" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30345884</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.moran.2012.235">Moran
|
|
A, O'Hara
|
|
C, Khan
|
|
S, Shack
|
|
L, Woodward
|
|
E, Maher
|
|
ER, Lalloo
|
|
F, Evans
|
|
DG. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations.
|
|
Fam Cancer.
|
|
2012;11:235-42.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22187320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22187320</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.nyberg.2020.24">Nyberg
|
|
T, Frost
|
|
D, Barrowdale
|
|
D, Evans
|
|
DG, Bancroft
|
|
E, Adlard
|
|
J, Ahmed
|
|
M, Barwell
|
|
J, Brady
|
|
AF, Brewer
|
|
C, Cook
|
|
J, Davidson
|
|
R, Donaldson
|
|
A, Eason
|
|
J, Gregory
|
|
H, Henderson
|
|
A, Izatt
|
|
L, Kennedy
|
|
MJ, Miller
|
|
C, Morrison
|
|
PJ, Murray
|
|
A, Ong
|
|
KR, Porteous
|
|
M, Pottinger
|
|
C, Rogers
|
|
MT, Side
|
|
L, Snape
|
|
K, Walker
|
|
L, Tischkowitz
|
|
M, Eeles
|
|
R, Easton
|
|
DF, Antoniou
|
|
AC. Prostate cancer risks for male BRCA1 and BRCA2 mutation carriers: a prospective cohort study.
|
|
Eur Urol.
|
|
2020;77:24-35.
|
|
[<a href="/pmc/articles/PMC6926480/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6926480</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31495749" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31495749</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.parmigiani.1998.145">Parmigiani
|
|
G, Berry
|
|
D, Aguilar
|
|
O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2.
|
|
Am J Hum Genet.
|
|
1998;62:145-58.
|
|
[<a href="/pmc/articles/PMC1376797/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1376797</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9443863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9443863</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.phelan.2002.352">Phelan
|
|
CM, Kwan
|
|
E, Jack
|
|
E, Li
|
|
S, Morgan
|
|
C, Aubé
|
|
J, Hanna
|
|
D, Narod
|
|
SA. A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families.
|
|
Hum Mutat.
|
|
2002;20:352-7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12402332" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12402332</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.phillips.2013.3091">Phillips
|
|
KA, Milne
|
|
RL, Rookus
|
|
MA, Daly
|
|
MB, Antoniou
|
|
AC, Peock
|
|
S, Frost
|
|
D, Easton
|
|
DF, Ellis
|
|
S, Friedlander
|
|
ML, Buys
|
|
SS, Andrieu
|
|
N, Noguès
|
|
C, Stoppa-Lyonnet
|
|
D, Bonadona
|
|
V, Pujol
|
|
P, McLachlan
|
|
SA, John
|
|
EM, Hooning
|
|
MJ, Seynaeve
|
|
C, Tollenaar
|
|
RA, Goldgar
|
|
DE, Terry
|
|
MB, Caldes
|
|
T, Weideman
|
|
PC, Andrulis
|
|
IL, Singer
|
|
CF, Birch
|
|
K, Simard
|
|
J, Southey
|
|
MC, Olsson
|
|
HL, Jakubowska
|
|
A, Olah
|
|
E, Gerdes
|
|
AM, Foretova
|
|
L, Hopper
|
|
JL. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
|
|
J Clin Oncol.
|
|
2013;31: 3091-9.
|
|
[<a href="/pmc/articles/PMC3753701/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3753701</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23918944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23918944</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.pierce.2006.2437">Pierce
|
|
LJ, Levin
|
|
AM, Rebbeck
|
|
TR, Ben-David
|
|
MA, Friedman
|
|
E, Solin
|
|
LJ, Harris
|
|
EE, Gaffney
|
|
DK, Haffty
|
|
BG, Dawson
|
|
LA, Narod
|
|
SA, Olivotto
|
|
IA, Eisen
|
|
A, Whelan
|
|
TJ, Olopade
|
|
OI, Isaacs
|
|
C, Merajver
|
|
SD, Wong
|
|
JS, Garber
|
|
JE, Weber
|
|
BL. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer.
|
|
J Clin Oncol.
|
|
2006;24:2437-43.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16636335" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16636335</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.rafnar.2004.2788">Rafnar
|
|
T, Benediktsdottir
|
|
KR, Eldon
|
|
BJ, Gestsson
|
|
T, Saemundsson
|
|
H, Olafsson
|
|
K, Salvarsdottir
|
|
A, Steingrimsson
|
|
E, Thorlacius
|
|
S. BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study.
|
|
Eur J Cancer.
|
|
2004;40:2788-93.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15571962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15571962</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.rakha.2008.2568">Rakha
|
|
EA, Reis-Filho
|
|
JS, Ellis
|
|
IO. Basal-like breast cancer: a critical review.
|
|
J Clin Oncol.
|
|
2008;26:2568-81.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18487574" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18487574</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.ramus.2015.djv214">Ramus
|
|
SJ, Song
|
|
H, Dicks
|
|
E, Tyrer
|
|
JP, Rosenthal
|
|
AN, Intermaggio
|
|
MP, Fraser
|
|
L, Gentry-Maharaj
|
|
A, Hayward
|
|
J, Philpott
|
|
S, Anderson
|
|
C, Edlund
|
|
CK, Conti
|
|
D, Harrington
|
|
P, Barrowdale
|
|
D, Bowtell
|
|
DD, Alsop
|
|
K, Mitchell
|
|
G, Cicek
|
|
MS, Cunningham
|
|
JM, Fridley
|
|
BL, Alsop
|
|
J, Jimenez-Linan
|
|
M, Poblete
|
|
S, Lele
|
|
S, Sucheston-Campbell
|
|
L, Moysich
|
|
KB, Sieh
|
|
W, McGuire
|
|
V, Lester
|
|
J, Bogdanova
|
|
N, Dürst
|
|
M, Hillemanns
|
|
P, Odunsi
|
|
K, Whittemore
|
|
AS, Karlan
|
|
BY, Dörk
|
|
T, Goode
|
|
EL, Menon
|
|
U, Jacobs
|
|
IJ, Antoniou
|
|
AC, Pharoah
|
|
PD, Gayther
|
|
SA, et al.
|
|
Germline Mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer.
|
|
J Natl Cancer Inst.
|
|
2015;107:djv214.
|
|
[<a href="/pmc/articles/PMC4643629/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4643629</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26315354" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26315354</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.rebbeck.2005.7804">Rebbeck
|
|
TR, Friebel
|
|
T, Wagner
|
|
T, Lynch
|
|
HT, Garber
|
|
JE, Daly
|
|
MB, Isaacs
|
|
C, Olopade
|
|
OI, Neuhausen
|
|
SL, van 't Veer
|
|
L, Eeles
|
|
R, Evans
|
|
DG, Tomlinson
|
|
G, Matloff
|
|
E, Narod
|
|
SA, Eisen
|
|
A, Domchek
|
|
S, Armstrong
|
|
K, Weber
|
|
BL, et al.
|
|
Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.
|
|
J Clin Oncol.
|
|
2005;23:7804-10
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16219936" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16219936</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.rebbeck.2015.1347">Rebbeck
|
|
TR, Mitra
|
|
N, Wan
|
|
F, Sinilnikova
|
|
OM, Healey
|
|
S, McGuffog
|
|
L, Mazoyer
|
|
S, Chenevix-Trench
|
|
G, Easton
|
|
DF, Antoniou
|
|
AC, Nathanson
|
|
KL, Laitman
|
|
Y, Kushnir
|
|
A, Paluch-Shimon
|
|
S, Berger
|
|
R, Zidan
|
|
J, Friedman
|
|
E, Ehrencrona
|
|
H, Stenmark-Askmalm
|
|
M, Einbeigi
|
|
Z, Loman
|
|
N, Harbst
|
|
K, Rantala
|
|
J, Melin
|
|
B, Huo
|
|
D, Olopade
|
|
OI, Seldon
|
|
J, Ganz
|
|
PA, Nussbaum
|
|
RL, Chan
|
|
SB, Odunsi
|
|
K, Gayther
|
|
SA, Domchek
|
|
SM, Arun
|
|
BK, Lu
|
|
KH, Mitchell
|
|
G, Karlan
|
|
BY, Walsh
|
|
C, Lester
|
|
J, Godwin
|
|
AK, Pathak
|
|
H, Ross
|
|
E, Daly
|
|
MB, Whittemore
|
|
AS, John
|
|
EM, Miron
|
|
A, Terry
|
|
MB, Chung
|
|
WK, Goldgar
|
|
DE, Buys
|
|
SS, Janavicius
|
|
R, Tihomirova
|
|
L, Tung
|
|
N, Dorfling
|
|
CM, van Rensburg
|
|
EJ, Steele
|
|
L, Neuhausen
|
|
SL, Ding
|
|
YC, Ejlertsen
|
|
B, Gerdes
|
|
AM, Hansen
|
|
TV, Ramón y Cajal
|
|
T, Osorio
|
|
A, Benitez
|
|
J, Godino
|
|
J, Tejada
|
|
MI, Duran
|
|
M, Weitzel
|
|
JN, Bobolis
|
|
KA, Sand
|
|
SR, Fontaine
|
|
A, Savarese
|
|
A, Pasini
|
|
B, Peissel
|
|
B, Bonanni
|
|
B, Zaffaroni
|
|
D, Vignolo-Lutati
|
|
F, Scuvera
|
|
G, Giannini
|
|
G, Bernard
|
|
L, Genuardi
|
|
M, Radice
|
|
P, Dolcetti
|
|
R, Manoukian
|
|
S, Pensotti
|
|
V, Gismondi
|
|
V, Yannoukakos
|
|
D, Fostira
|
|
F, Garber
|
|
J, Torres
|
|
D, Rashid
|
|
MU, Hamann
|
|
U, Peock
|
|
S, Frost
|
|
D, Platte
|
|
R, Evans
|
|
DG, Eeles
|
|
R, Davidson
|
|
R, Eccles
|
|
D, Cole
|
|
T, Cook
|
|
J, Brewer
|
|
C, Hodgson
|
|
S, Morrison
|
|
PJ, Walker
|
|
L, Porteous
|
|
ME, Kennedy
|
|
MJ, Izatt
|
|
L, Adlard
|
|
J, Donaldson
|
|
A, Ellis
|
|
S, Sharma
|
|
P, Schmutzler
|
|
RK, Wappenschmidt
|
|
B, Becker
|
|
A, Rhiem
|
|
K, Hahnen
|
|
E, Engel
|
|
C, Meindl
|
|
A, Engert
|
|
S, Ditsch
|
|
N, Arnold
|
|
N, Plendl
|
|
HJ, Mundhenke
|
|
C, Niederacher
|
|
D, Fleisch
|
|
M, Sutter
|
|
C, Bartram
|
|
CR, Dikow
|
|
N, Wang-Gohrke
|
|
S, Gadzicki
|
|
D, Steinemann
|
|
D, Kast
|
|
K, Beer
|
|
M, Varon-Mateeva
|
|
R, Gehrig
|
|
A, Weber
|
|
BH, Stoppa-Lyonnet
|
|
D, Sinilnikova
|
|
OM, Mazoyer
|
|
S, Houdayer
|
|
C, Belotti
|
|
M, Gauthier-Villars
|
|
M, Damiola
|
|
F, Boutry-Kryza
|
|
N, Lasset
|
|
C, Sobol
|
|
H, Peyrat
|
|
JP, Muller
|
|
D, Fricker
|
|
JP, Collonge-Rame
|
|
MA, Mortemousque
|
|
I, Nogues
|
|
C, Rouleau
|
|
E, Isaacs
|
|
C, De Paepe
|
|
A, Poppe
|
|
B, Claes
|
|
K, De Leeneer
|
|
K, Piedmonte
|
|
M, Rodriguez
|
|
G, Wakely
|
|
K, Boggess
|
|
J, Blank
|
|
SV, Basil
|
|
J, Azodi
|
|
M, Phillips
|
|
KA, Caldes
|
|
T, de la Hoya
|
|
M, Romero
|
|
A, Nevanlinna
|
|
H, Aittomäki
|
|
K, van der Hout
|
|
AH, Hogervorst
|
|
FB, Verhoef
|
|
S, Collée
|
|
JM, Seynaeve
|
|
C, Oosterwijk
|
|
JC, Gille
|
|
JJ, Wijnen
|
|
JT, Gómez Garcia
|
|
EB, Kets
|
|
CM, Ausems
|
|
MG, Aalfs
|
|
CM, Devilee
|
|
P, Mensenkamp
|
|
AR, Kwong
|
|
A, Olah
|
|
E, Papp
|
|
J, Diez
|
|
O, Lazaro
|
|
C, Darder
|
|
E, Blanco
|
|
I, Salinas
|
|
M, Jakubowska
|
|
A, Lubinski
|
|
J, Gronwald
|
|
J, Jaworska-Bieniek
|
|
K, Durda
|
|
K, Sukiennicki
|
|
G, Huzarski
|
|
T, Byrski
|
|
T, Cybulski
|
|
C, Toloczko-Grabarek
|
|
A, Złowocka-Perłowska
|
|
E, Menkiszak
|
|
J, Arason
|
|
A, Barkardottir
|
|
RB, Simard
|
|
J, Laframboise
|
|
R, Montagna
|
|
M, Agata
|
|
S, Alducci
|
|
E, Peixoto
|
|
A, Teixeira
|
|
MR, Spurdle
|
|
AB, Lee
|
|
MH, Park
|
|
SK, Kim
|
|
SW, Friebel
|
|
TM, Couch
|
|
FJ, Lindor
|
|
NM, Pankratz
|
|
VS, Guidugli
|
|
L, Wang
|
|
X, Tischkowitz
|
|
M, Foretova
|
|
L, Vijai
|
|
J, Offit
|
|
K, Robson
|
|
M, Rau-Murthy
|
|
R, Kauff
|
|
N, Fink-Retter
|
|
A, Singer
|
|
CF, Rappaport
|
|
C, Gschwantler-Kaulich
|
|
D, Pfeiler
|
|
G, Tea
|
|
MK, Berger
|
|
A, Greene
|
|
MH, Mai
|
|
PL, Imyanitov
|
|
EN, Toland
|
|
AE, Senter
|
|
L, Bojesen
|
|
A, Pedersen
|
|
IS, Skytte
|
|
AB, Sunde
|
|
L, Thomassen
|
|
M, Moeller
|
|
ST, Kruse
|
|
TA, Jensen
|
|
UB, Caligo
|
|
MA, Aretini
|
|
P, Teo
|
|
SH, Selkirk
|
|
CG, Hulick
|
|
PJ, Andrulis
|
|
I, et al.
|
|
Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.
|
|
JAMA. 2015;313:1347-61.
|
|
[<a href="/pmc/articles/PMC4537700/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4537700</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25849179" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25849179</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.reiner.2020.1275">Reiner
|
|
AS, Robson
|
|
ME, Mellemkjær
|
|
L, Tischkowitz
|
|
M, John
|
|
EM, Lynch
|
|
CF, Brooks
|
|
JD, Boice
|
|
JD, Knight
|
|
JA, Teraoka
|
|
SN, Liang
|
|
X, Woods
|
|
M, Shen
|
|
R, Shore
|
|
RE, Stram
|
|
DO, Thomas
|
|
DC, Malone
|
|
KE, Bernstein
|
|
L, Riaz
|
|
N, Woodward
|
|
W, Powell
|
|
S, Goldgar
|
|
D, Concannon
|
|
P, Bernstein
|
|
JL, et al.
|
|
Radiation treatment, ATM, BRCA1/2, and CHEK2*1100delC pathogenic variants and risk of contralateral breast cancer.
|
|
J Natl Cancer Inst.
|
|
2020;112:1275-9.
|
|
[<a href="/pmc/articles/PMC7735763/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7735763</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32119081" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32119081</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.richards.2015.405">Richards
|
|
S, Aziz
|
|
N, Bale
|
|
S, Bick
|
|
D, Das
|
|
S, Gastier-Foster
|
|
J, Grody
|
|
WW, Hegde
|
|
M, Lyon
|
|
E, Spector
|
|
E, Voelkerding
|
|
K, Rehm
|
|
HL, et al.
|
|
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
|
Genet Med.
|
|
2015;17:405-24.
|
|
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.risch.2006.1694">Risch
|
|
HA, McLaughlin
|
|
JR, Cole
|
|
DE, Rosen
|
|
B, Bradley
|
|
L, Fan
|
|
I, Tang
|
|
J, Li
|
|
S, Zhang
|
|
S, Shaw
|
|
PA, Narod
|
|
SA.Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada.
|
|
J Natl Cancer Inst.
|
|
2006;98:1694-706.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17148771" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17148771</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.robson.2017.523">Robson
|
|
M, Im
|
|
SA, Senkus
|
|
E, Xu
|
|
B, Domchek
|
|
SM, Masuda
|
|
N, Delaloge
|
|
S, Li
|
|
W, Tung
|
|
N, Armstrong
|
|
A, Wu
|
|
W, Goessl
|
|
C, Runswick
|
|
S, Conte
|
|
P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation.
|
|
N Engl J Med.
|
|
2017;377:523-33.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28578601" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28578601</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.robson.2005.44">Robson
|
|
M, Svahn
|
|
T, McCormick
|
|
B, Borgen
|
|
P, Hudis
|
|
CA, Norton
|
|
L, Offit
|
|
K. Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series.
|
|
Cancer.
|
|
2005;103:44-51.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15558796" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15558796</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.robson.2004.r8">Robson
|
|
ME, Chappuis
|
|
PO, Satagopan
|
|
J, Wong
|
|
N, Boyd
|
|
J, Goffin
|
|
JR, Hudis
|
|
C, Roberge
|
|
D, Norton
|
|
L, Bégin
|
|
LR, Offit
|
|
K, Foulkes
|
|
WD. A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment.
|
|
Breast Cancer Res.
|
|
2004;6:R8-R17.
|
|
[<a href="/pmc/articles/PMC314444/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC314444</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14680495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14680495</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.rosen.2006.175">Rosen
|
|
EM, Fan
|
|
S, Ma
|
|
X. BRCA1 regulation of transcription.
|
|
Cancer Lett.
|
|
2006;236:175-85
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15975711" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15975711</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.sankaran.2006.4100">Sankaran
|
|
S, Starita
|
|
LM, Simons
|
|
AM, Parvin
|
|
JD. Identification of domains of BRCA1 critical for the ubiquitin-dependent inhibition of centrosome function.
|
|
Cancer Res.
|
|
2006;66:4100-7
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16618730" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16618730</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.satagopan.2002.3776">Satagopan
|
|
JM, Boyd
|
|
J, Kauff
|
|
ND, Robson
|
|
M, Scheuer
|
|
L, Narod
|
|
S, Offit
|
|
K. Ovarian cancer risk in Ashkenazi Jewish carrier of BRCA1 and BRCA2 mutations.
|
|
Clin Cancer Res.
|
|
2002;8:3776-81.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12473589" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12473589</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.seynaeve.2004.1150">Seynaeve
|
|
C, Verhoog
|
|
LC, van de Bosch
|
|
LM, van Geel
|
|
AN, Menke-Pluymers
|
|
M, Meijers-Heijboer
|
|
EJ, van den Ouweland
|
|
AM, Wagner
|
|
A, Creutzberg
|
|
CL, Niermeijer
|
|
MF, Klijn
|
|
JG, Brekelmans
|
|
CT. Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy.
|
|
Eur J Cancer.
|
|
2004;40:1150-8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15110878" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15110878</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.spurdle.2012.525">Spurdle
|
|
AB, Whiley
|
|
PJ, Thompson
|
|
B, Feng
|
|
B, Healey
|
|
S, Brown
|
|
MA, Pettigrew
|
|
C, Van Asperen
|
|
CJ, Ausems
|
|
MG, Kattentidt-Mouravieva
|
|
AA, van den Ouweland
|
|
AM, Lindblom
|
|
A, Pigg
|
|
MH, Schmutzler
|
|
RK, Engel
|
|
C, Meindl
|
|
A, Caputo
|
|
S, Sinilnikova
|
|
OM, Lidereau
|
|
R, Couch
|
|
FJ, Guidugli
|
|
L, Hansen
|
|
TV, Thomassen
|
|
M, Eccles
|
|
DM, Tucker
|
|
K, Benitez
|
|
J, Domchek
|
|
SM, Toland
|
|
AE, Van Rensburg
|
|
EJ, Wappenschmidt
|
|
B, Borg
|
|
Å, Vreeswijk
|
|
MP, Goldgar
|
|
DE, et al.
|
|
BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk.
|
|
J Med Genet.
|
|
2012;49:525-32.
|
|
[<a href="/pmc/articles/PMC3810416/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3810416</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22889855" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22889855</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.struewing.1997.1401">Struewing
|
|
JP, Hartge
|
|
P, Wacholder
|
|
S, Baker
|
|
SM, Berlin
|
|
M, McAdams
|
|
M, Timmerman
|
|
MM, Brody
|
|
LC, Tucker
|
|
MA. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
|
|
N Engl J Med.
|
|
1997;336:1401-8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9145676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9145676</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.swanson.2016.20">Swanson
|
|
CL, Bakkum-Gamez
|
|
JN. Options in prophylactic surgery to prevent ovarian cancer in high-risk women. How new hypotheses of fallopian tube origin influence recommendations.
|
|
Curr Treat Options Oncol.
|
|
2016;17:20.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27032642" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27032642</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.tai.2007.1811">Tai
|
|
YC, Domchek
|
|
S, Parmigiani
|
|
G, Chen
|
|
S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.
|
|
J Natl Cancer Inst.
|
|
2007;99:1811-4.
|
|
[<a href="/pmc/articles/PMC2267289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2267289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18042939" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18042939</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.thompson.2002.1358">Thompson
|
|
D, Easton
|
|
DF. The breast cancer linkage consortium. Cancer incidence in BRCA1 mutation carriers.
|
|
J Natl Cancer Inst.
|
|
2002;94:1358-65.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12237281" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12237281</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.truty.2019.114">Truty
|
|
R, Paul
|
|
J, Kennemer
|
|
M, Lincoln
|
|
SE, Olivares
|
|
E, Nussbaum
|
|
RL, Aradhya
|
|
S. Prevalence and properties of intragenic copy-number variation in Mendelian disease genes.
|
|
Genet Med.
|
|
2019;21:114-23.
|
|
[<a href="/pmc/articles/PMC6752305/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6752305</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29895855" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29895855</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.tutt.2021.2394">Tutt
|
|
ANJ, Garber
|
|
JE, Kaufman
|
|
B, Viale
|
|
G, Fumagalli
|
|
D, Rastogi
|
|
P, Gelber
|
|
RD, de Azambuja
|
|
E, Fielding
|
|
A, Balmaña
|
|
J, Domchek
|
|
SM, Gelmon
|
|
KA, Hollingsworth
|
|
SJ, Korde
|
|
LA, Linderholm
|
|
B, Bandos
|
|
H, Senkus
|
|
E, Suga
|
|
JM, Shao
|
|
Z, Pippas
|
|
AW, Nowecki
|
|
Z, Huzarski
|
|
T, Ganz
|
|
PA, Lucas
|
|
PC, Baker
|
|
N, Loibl
|
|
S, McConnell
|
|
R, Piccart
|
|
M, Schmutzler
|
|
R, Steger
|
|
GG, Costantino
|
|
JP, Arahmani
|
|
A, Wolmark
|
|
N, McFadden
|
|
E, Karantza
|
|
V, Lakhani
|
|
SR, Yothers
|
|
G, Campbell
|
|
C, Geyer
|
|
CE
|
|
Jr, et al.
|
|
Adjuvant olaparib for patients with BRCA1-or BRCA2-mutated breast cancer.
|
|
N Engl J Med.
|
|
2021;384:2394-405.
|
|
[<a href="/pmc/articles/PMC9126186/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9126186</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34081848" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34081848</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.tyrer.2004.1111">Tyrer
|
|
J, Duffy
|
|
SW, Cuzick
|
|
J. A breast cancer prediction model incorporating familial and personal risk factors.
|
|
Stat Med.
|
|
2004;23:1111-30
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15057881" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15057881</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.van_asperen.2005.711">van Asperen
|
|
CJ, Brohet
|
|
RM, Meijers-Heijboer
|
|
EJ, Hoogerbrugge
|
|
N, Verhoef
|
|
S, Vasen
|
|
HF, Ausems
|
|
MG, Menko
|
|
FH, Gomez Garcia
|
|
EB, Klijn
|
|
JG, Hogervorst
|
|
FB, van Houwelingen
|
|
JC, van't Veer
|
|
LJ, Rookus
|
|
MA, van Leeuwen
|
|
FE, et al.
|
|
Cancer risks in BRCA2 families: estimates for sites other than breast and ovary.
|
|
J Med Genet . 2005;42:711-9.
|
|
[<a href="/pmc/articles/PMC1736136/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1736136</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16141007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16141007</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.van_den_broek.2015.e0120189">van den Broek
|
|
AJ, Schmidt
|
|
MK, van 't Veer
|
|
LJ, Tollenaar
|
|
RA, van Leeuwen
|
|
FE. Worse breast cancer prognosis of BRCA1/BRCA2 mutation carriers: what's the evidence? A systematic review with meta-analysis.
|
|
PLoS One.
|
|
2015;10:e0120189.
|
|
[<a href="/pmc/articles/PMC4376645/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4376645</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25816289" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25816289</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.van_den_broek.2016.409">van den Broek
|
|
AJ, van 't Veer
|
|
LJ, Hooning
|
|
MJ, Cornelissen
|
|
S, Broeks
|
|
A, Rutgers
|
|
EJ, Smit
|
|
VT, Cornelisse
|
|
CJ, van Beek
|
|
M, Janssen-Heijnen
|
|
ML, Seynaeve
|
|
C, Westenend
|
|
PJ, Jobsen
|
|
JJ, Siesling
|
|
S, Tollenaar
|
|
RA, van Leeuwen
|
|
FE, Schmidt
|
|
MK. Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers.
|
|
J Clin Oncol.
|
|
2016;34:409-18.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26700119" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26700119</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.van_der_kolk.2010.643">van der Kolk
|
|
DM, de Bock
|
|
GH, Leegte
|
|
BK, Schaapveld
|
|
M, Mourits
|
|
JE, de Vries
|
|
J, van der Hout
|
|
AH, Oosterwijk
|
|
JC. Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age.
|
|
Breast Cancer Res Treat.
|
|
2010;124:643-51.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/20204502" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20204502</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.venkitaraman.2002.171">Venkitaraman
|
|
AR. Cancer susceptibility and the functions of BRCA1 and BRCA2.
|
|
Cell.
|
|
2002;108:171-82
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11832208" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11832208</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.verhoog.2000.119s">Verhoog
|
|
LC, Berns
|
|
EM, Brekelmans
|
|
CT, Seynaeve
|
|
C, Meijers-Heijboer
|
|
EJ, Klijn
|
|
JG. Prognostic significance of germline BRCA2 mutations in hereditary breast cancer patients.
|
|
J Clin Oncol.
|
|
2000;18:119S-24S.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11060339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11060339</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.vichapat.2012.3478">Vichapat
|
|
V, Garmo
|
|
H, Holmqusit
|
|
M, Liljegren
|
|
G, Warnberg
|
|
F, Llambe
|
|
M, Fornander
|
|
T, Adolfsson
|
|
J, Luchtenborg
|
|
M, Holmberg
|
|
L. Tumor stage affects risk and prognosis of contralateral breast cancer: results from a large Swedish-population-based study.
|
|
J Clin Oncol.
|
|
2012;30:3478-85.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22927521" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22927521</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.weischer.2007.57">Weischer
|
|
M, Bojesen
|
|
SE, Tybjaerg-Hansen
|
|
A, Axelsson
|
|
CK, Nordestgaard
|
|
BG. Increased risk of breast cancer associated with CHEK2*1100delC.
|
|
J Clin Oncol.
|
|
2007;25:57-63.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16880452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16880452</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.whittemore.2004.2078">Whittemore
|
|
AS, Gong
|
|
G, John
|
|
EM, McGuire
|
|
V, Li
|
|
FP, Ostrow
|
|
KL, Dicioccio
|
|
R, Felberg
|
|
A, West
|
|
DW. Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic whites.
|
|
Cancer Epidemiol Biomarkers Prev.
|
|
2004;13:2078-83.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15598764" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15598764</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.yang.2020.674">Yang
|
|
X, Leslie
|
|
G, Doroszuk
|
|
A, Schneider
|
|
S, Allen
|
|
J, Decker
|
|
B, Dunning
|
|
AM, Redman
|
|
J, Scarth
|
|
J, Plaskocinska
|
|
I, Luccarini
|
|
C, Shah
|
|
M, Pooley
|
|
K, Dorling
|
|
L, Lee
|
|
A, Adank
|
|
MA, Adlard
|
|
J, Aittomäki
|
|
K, Andrulis
|
|
IL, Ang
|
|
P, Barwell
|
|
J, Bernstein
|
|
JL, Bobolis
|
|
K, Borg
|
|
Å, Blomqvist
|
|
C, Claes
|
|
KBM, Concannon
|
|
P, Cuggia
|
|
A, Culver
|
|
JO, Damiola
|
|
F, de Pauw
|
|
A, Diez
|
|
O, Dolinsky
|
|
JS, Domchek
|
|
SM, Engel
|
|
C, Evans
|
|
DG, Fostira
|
|
F, Garber
|
|
J, Golmard
|
|
L, Goode
|
|
EL, Gruber
|
|
SB, Hahnen
|
|
E, Hake
|
|
C, Heikkinen
|
|
T, Hurley
|
|
JE, Janavicius
|
|
R, Kleibl
|
|
Z, Kleiblova
|
|
P, Konstantopoulou
|
|
I, Kvist
|
|
A, Laduca
|
|
H, Lee
|
|
ASG, Lesueur
|
|
F, Maher
|
|
ER, Mannermaa
|
|
A, Manoukian
|
|
S, McFarland
|
|
R, McKinnon
|
|
W, Meindl
|
|
A, Metcalfe
|
|
K, Mohd Taib
|
|
NA, Moilanen
|
|
J, Nathanson
|
|
KL, Neuhausen
|
|
S, Ng
|
|
PS, Nguyen-Dumont
|
|
T, Nielsen
|
|
SM, Obermair
|
|
F, Offit
|
|
K, Olopade
|
|
OI, Ottini
|
|
L, Penkert
|
|
J, Pylkäs
|
|
K, Radice
|
|
P, Ramus
|
|
SJ, Rudaitis
|
|
V, Side
|
|
L, Silva-Smith
|
|
R, Silvestri
|
|
V, Skytte
|
|
AB, Slavin
|
|
T, Soukupova
|
|
J, Tondini
|
|
C, Trainer
|
|
AH, Unzeitig
|
|
G, Usha
|
|
L, van Overeem Hansen
|
|
T, Whitworth
|
|
J, Wood
|
|
M, Yip
|
|
CH, Yoon
|
|
SY, Yussuf
|
|
A, Zogopoulos
|
|
G, Goldgar
|
|
D, Hopper
|
|
JL, Chenevix-Trench
|
|
G, Pharoah
|
|
P, George
|
|
SHL, Balmaña
|
|
J, Houdayer
|
|
C, James
|
|
P, El-Haffaf
|
|
Z, Ehrencrona
|
|
H, Janatova
|
|
M, Peterlongo
|
|
P, Nevanlinna
|
|
H, Schmutzler
|
|
R, Teo
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SH, Robson
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M, Pal
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T, Couch
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F, Weitzel
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JN, Elliott
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A, Southey
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M, Winqvist
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R, Easton
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DF, Foulkes
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WD, Antoniou
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AC, Tischkowitz
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M. Cancer Risks associated with germline PALB2 pathogenic variants: an international study of 524 families.
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J Clin Oncol.
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2020;38:674-85.
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[<a href="/pmc/articles/PMC7049229/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7049229</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31841383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31841383</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.yates.2011.463">Yates
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MS, Meyer
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LA, Deavers
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MT, Daniels
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MS, Keeler
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ER, Mok
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SC, Gershenson
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DM, Lu
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KH. Microscopic and early-stage ovarian cancers in BRCA1/2 mutation carriers: building a model for early BRCA-associated tumorigenesis.
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Cancer Prev Res (Phila). 2011;4:463-70.
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[<a href="/pmc/articles/PMC3048908/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3048908</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21278312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21278312</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="brca1.REF.zhong.2015.211">Zhong
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Q, Peng
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HL, Zhao
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X, Zhang
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L, Hwang
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WT. Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis.
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Clin Cancer Res.
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2015;21:211-20.
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[<a href="/pmc/articles/PMC4286460/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4286460</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25348513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25348513</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1247_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Nancie Petrucelli</span>, MS<div class="affiliation small">Wayne State University School of Medicine/Detroit Medical Center;Cancer Genetic Counseling ServiceKarmanos Cancer InstituteDetroit, Michigan<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.sonamrak@lecurtep" class="oemail">gro.sonamrak@lecurtep</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Mary B Daly</span>, MD, PhD<div class="affiliation small">Chair, Department of Clinical GeneticsFox Chase Cancer CenterPhiladelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.cccf@ylad.yram" class="oemail">ude.cccf@ylad.yram</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Tuya Pal</span>, MD<div class="affiliation small">Vanderbilt-Ingram Cancer CenterNashville, Tennessee<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.cmuv@lap.ayut" class="oemail">gro.cmuv@lap.ayut</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">September 4, 1998</span>; Last Revision: <span itemprop="dateModified">September 21, 2023</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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hereby granted to reproduce, distribute, and translate copies of content materials for
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noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
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of GeneReviews chapters for use in lab reports and clinic notes are a permitted
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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2023 Sep 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/bcl11a-id/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/spg17/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobbrca1Tmoleculargenetictestingusedi"><div id="brca1.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>BRCA1-</i> and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of <i>BRCA1</i>- & <i>BRCA2</i>-Associated HBOC Attributed to Pathogenic Variants in Gene</th><th id="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detected by Method</th></tr><tr><th headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></th><th headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA1</i>
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</td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">66%</td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">87%-89% <sup>5</sup></td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11%-13% <sup>5</sup></td></tr><tr><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA2</i>
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</td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34%</td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%-98% <sup>5</sup></td><td headers="hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_brca1.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2%-3% <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">HBOC = hereditary breast and ovarian cancer</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="brca1.TF.1.1"><p class="no_margin">See <a href="/books/NBK1247/?report=reader#brca1.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="brca1.TF.1.2"><p class="no_margin">See <a href="#brca1.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="brca1.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="brca1.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="brca1.TF.1.5"><p class="no_margin"><a class="bibr" href="#brca1.REF.truty.2019.114" rid="brca1.REF.truty.2019.114">Truty et al [2019]</a>, <a class="bibr" href="#brca1.REF.laduca.2020.407" rid="brca1.REF.laduca.2020.407">LaDuca et al [2020]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1Triskofmalignancyinindividual"><div id="brca1.T.risk_of_malignancy_in_individual" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Risk of Malignancy in Individuals with a Germline <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variant</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.risk_of_malignancy_in_individual/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.risk_of_malignancy_in_individual_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" style="text-align:left;vertical-align:middle;">Cancer Type</th><th id="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" style="text-align:left;vertical-align:middle;">General Population Risk</th><th id="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Risk for Malignancy <sup>1</sup></th></tr><tr><th headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3" id="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA1</i>
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</th><th headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3" id="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA2</i>
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</th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Breast</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">55%-72% by age 70</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">45%-69%</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Contralateral breast cancer</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2% w/in 5 yrs</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">20%-30% w/in 10 yrs; 40%-50% w/in 20 yrs</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ovarian</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-2%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39%-44%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11%-17%</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Male breast</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.1%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-2%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6%-8%</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Prostate</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6% by age 69 yrs</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21% by age 75 yrs;<br />29% by age 85 yrs</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27% by age 75 yrs;<br />60% by age 85 yrs</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Pancreatic</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-3%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3%-5% by age 70 yrs</td></tr><tr><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Melanoma (cutaneous & ocular)</b>
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</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.6%</td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_1_3 hd_h_brca1.T.risk_of_malignancy_in_individual_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Elevated risk</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="brca1.TF.2.1"><p class="no_margin"><a class="bibr" href="#brca1.REF.verhoog.2000.119s" rid="brca1.REF.verhoog.2000.119s">Verhoog et al [2000]</a>, <a class="bibr" href="#brca1.REF.brose.2002.1365" rid="brca1.REF.brose.2002.1365">Brose et al [2002]</a>, <a class="bibr" href="#brca1.REF.satagopan.2002.3776" rid="brca1.REF.satagopan.2002.3776">Satagopan et al [2002]</a>, <a class="bibr" href="#brca1.REF.thompson.2002.1358" rid="brca1.REF.thompson.2002.1358">Thompson & Easton [2002]</a>, <a class="bibr" href="#brca1.REF.antoniou.2003.1117" rid="brca1.REF.antoniou.2003.1117">Antoniou et al [2003]</a>, <a class="bibr" href="#brca1.REF.hearle.2003.458" rid="brca1.REF.hearle.2003.458">Hearle et al [2003]</a>, <a class="bibr" href="#brca1.REF.kirova.2005.2304" rid="brca1.REF.kirova.2005.2304">Kirova et al [2005]</a>, <a class="bibr" href="#brca1.REF.robson.2005.44" rid="brca1.REF.robson.2005.44">Robson et al [2005]</a>, <a class="bibr" href="#brca1.REF.van_asperen.2005.711" rid="brca1.REF.van_asperen.2005.711">van Asperen et al [2005]</a>, <a class="bibr" href="#brca1.REF.chen.2006.863" rid="brca1.REF.chen.2006.863">Chen et al [2006]</a>, <a class="bibr" href="#brca1.REF.risch.2006.1694" rid="brca1.REF.risch.2006.1694">Risch et al [2006]</a>, <a class="bibr" href="#brca1.REF.chen.2007.1329" rid="brca1.REF.chen.2007.1329">Chen & Parmigiani [2007]</a>, <a class="bibr" href="#brca1.REF.tai.2007.1811" rid="brca1.REF.tai.2007.1811">Tai et al [2007]</a>, <a class="bibr" href="#brca1.REF.graeser.2009.5887" rid="brca1.REF.graeser.2009.5887">Graeser et al [2009]</a>, <a class="bibr" href="#brca1.REF.evans.2010.710" rid="brca1.REF.evans.2010.710">Evans et al [2010]</a>, <a class="bibr" href="#brca1.REF.van_der_kolk.2010.643" rid="brca1.REF.van_der_kolk.2010.643">van der Kolk et al [2010]</a>, <a class="bibr" href="#brca1.REF.kotejarai.2011.1230" rid="brca1.REF.kotejarai.2011.1230">Kote-Jarai et al [2011]</a>, <a class="bibr" href="#brca1.REF.iqbal.2012.2005" rid="brca1.REF.iqbal.2012.2005">Iqbal et al [2012]</a>, <a class="bibr" href="#brca1.REF.leongamornlert.2012.1697" rid="brca1.REF.leongamornlert.2012.1697">Leongamornlert et al [2012]</a>, <a class="bibr" href="#brca1.REF.moran.2012.235" rid="brca1.REF.moran.2012.235">Moran et al [2012]</a>, <a class="bibr" href="#brca1.REF.mavaddat.2013.812" rid="brca1.REF.mavaddat.2013.812">Mavaddat et al [2013]</a>, <a class="bibr" href="#brca1.REF.molinamontes.2014.721" rid="brca1.REF.molinamontes.2014.721">Molina-Montes et al [2014]</a>, <a class="bibr" href="#brca1.REF.basu.2015.531" rid="brca1.REF.basu.2015.531">Basu et al [2015]</a>, <a class="bibr" href="#brca1.REF.van_den_broek.2015.e0120189" rid="brca1.REF.van_den_broek.2015.e0120189">van den Broek et al [2015]</a>, <a class="bibr" href="#brca1.REF.van_den_broek.2016.409" rid="brca1.REF.van_den_broek.2016.409">van den Broek et al [2016]</a>, <a class="bibr" href="#brca1.REF.kuchenbaecker.2017.2402" rid="brca1.REF.kuchenbaecker.2017.2402">Kuchenbaecker et al [2017]</a>, <a class="bibr" href="#brca1.REF.nyberg.2020.24" rid="brca1.REF.nyberg.2020.24">Nyberg et al [2020]</a>, <a class="bibr" href="#brca1.REF.reiner.2020.1275" rid="brca1.REF.reiner.2020.1275">Reiner et al [2020]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1Tgenesassociatedwithcancersus"><div id="brca1.T.genes_associated_with_cancer_sus" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes Associated with Cancer Susceptibility to Consider in the Differential Diagnosis of <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.genes_associated_with_cancer_sus/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.genes_associated_with_cancer_sus_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cancer Susceptibility Syndrome</th><th id="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Associated Cancers / Distinctive Features</th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" colspan="4" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>High-penetrance (high-risk) genes for breast cancer</b>
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</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ATM</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATM</i> c.7271T>G</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Specific <i>ATM</i> pathogenic variants (e.g., c.7271T>G) are assoc w/high-penetrance breast cancer; heterozygosity for most other <i>ATM</i> pathogenic variants is assoc w/moderate-penetrance breast cancer (see below). <sup>1</sup></td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CDH1</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hgc/?report=reader">Hereditary diffuse gastric cancer</a>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer (lobular), diffuse gastric cancer. Majority of cancers occur before age 40 yrs.</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PALB2</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PALB2</i>-related cancer susceptibility (<a href="https://omim.org/entry/620442" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM 620442</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer ≤58%, <sup>2</sup> ovarian cancer, male breast cancer, pancreatic cancer</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PTEN</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/phts/?report=reader"><i>PTEN</i> hamartoma tumor syndrome</a>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer. Other cancers: thyroid, renal cell carcinoma, endometrial, colorectal. Multiple hamartomas, macrocephaly, trichilemmomas, papillomatous papules. Affected persons usually present by late 20s.</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>STK11</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/pjs/?report=reader">Peutz-Jeghers syndrome</a>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer. Other cancers: GI, ovarian (mostly SCTAT), cervical (adenoma malignum), pancreatic, Sertoli cell testicular. GI polyposis, mucocutaneous pigmentation, hyperpigmented macules on fingers.</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TP53</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/li-fraumeni/?report=reader">Li-Fraumeni syndrome</a>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer (often premenopausal). Other cancers: soft tissue sarcoma, osteosarcoma, brain, adrenocortical carcinoma, leukemias. Early-onset & multiple primary cancers.</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3 hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" colspan="4" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Moderate-penetrance (moderate-risk) genes for breast &/or ovarian cancer</b>
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</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATM</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATM</i>-related cancer susceptibility (<i>ATM</i> heterozygotes; see <a href="/books/n/gene/ataxia-telangiectas/?report=reader">Ataxia-Telangiectasia</a>.)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Specific <i>ATM</i> pathogenic variants, most notably c.7271T>G, are assoc w/high-penetrance breast cancer; heterozygosity for most other <i>ATM</i> pathogenic variants is assoc w/moderate-penetrance breast cancer. ↑ risk for other types of tumors such as pancreatic cancer & prostate cancer.</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BARD1</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>BARD1</i>-related cancer susceptibility (OMIM <a href="https://omim.org/entry/114480" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">114480</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRIP1</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>BRIP1</i>-related cancer susceptibility (OMIM <a href="https://omim.org/entry/605882" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">605882</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Epithelial ovarian cancer, <sup>3</sup> possible ↑ risk for breast cancer</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHEK2</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CHEK2</i>-related cancer susceptibility (OMIM <a href="https://omim.org/entry/604373" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">604373</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast cancer <sup>4</sup></td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EPCAM</i>
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<br />
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<i>MLH1</i>
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<br />
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<i>MSH2</i>
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<br />
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<i>MSH6</i>
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<br />
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<i>PMS2</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hnpcc/?report=reader">Lynch syndrome</a>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ovarian cancer, slightly ↑ risk for breast cancer. Colorectal polyps, endometrial cancer, gastric cancer, & other cancers. <sup>5</sup></td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>RAD51C</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>RAD51C</i>-related cancer susceptibility (OMIM <a href="https://omim.org/entry/613399" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613399</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ovarian cancer, possibly breast cancer (particularly ER/PR negative breast cancer)</td></tr><tr><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>RAD51D</i>
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</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>RAD51D</i>-related cancer susceptibility (OMIM <a href="https://omim.org/entry/614291" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614291</a>)</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_brca1.T.genes_associated_with_cancer_sus_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ovarian cancer, possibly breast cancer (particularly ER/PR negative breast cancer)</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">AD = autosomal dominant; ER = estrogen receptor; GI = gastrointestinal; MOI = mode of inheritance; PR = progesterone receptor; SCTAT = sex cord tumor with annular tubules</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="brca1.TF.3.1"><p class="no_margin">NCCN Guidelines, <a href="https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1503" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Version 3.2023</a> (accessed 8-17-23)</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="brca1.TF.3.2"><p class="no_margin"><a class="bibr" href="#brca1.REF.antoniou.2014.497" rid="brca1.REF.antoniou.2014.497">Antoniou et al [2014]</a>, <a class="bibr" href="#brca1.REF.yang.2020.674" rid="brca1.REF.yang.2020.674">Yang et al [2020]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="brca1.TF.3.3"><p class="no_margin">
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<a class="bibr" href="#brca1.REF.ramus.2015.djv214" rid="brca1.REF.ramus.2015.djv214">Ramus et al [2015]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="brca1.TF.3.4"><p class="no_margin">The <i>CHEK2</i> variant c.1100delC (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_007194.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_007194<wbr style="display:inline-block"></wbr>​.3</a>) is associated with an estimated two- to threefold increased breast cancer risk in women and a tenfold increased risk in men [CHEK2 Consortium 2004, <a class="bibr" href="#brca1.REF.bernstein.2006.348" rid="brca1.REF.bernstein.2006.348">Bernstein et al 2006</a>, <a class="bibr" href="#brca1.REF.weischer.2007.57" rid="brca1.REF.weischer.2007.57">Weischer et al 2007</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="brca1.TF.3.5"><p class="no_margin">Note regarding <i>PMS2</i>: Although studies have suggested a 3% lifetime risk for ovarian cancer that is higher than the observed risk in the general population, studies that specifically examine risks among individuals with <i>PMS2</i> pathogenic variants have not demonstrated a statistically significant relative increased risk for ovarian cancer.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1Trecommendedsurveillanceforwom"><div id="brca1.T.recommended_surveillance_for_wom" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Surveillance for Women with <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_wom/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.recommended_surveillance_for_wom_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Breast cancer</b>
|
|
</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast self-exam</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monthly</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical breast exam</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos beginning at age 25 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Mammogram</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 30 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Breast MRI</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 25 yrs or earlier if breast cancer was diagnosed in family member < age 30 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ovarian cancer</b>
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</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screening not recommended <sup>1</sup></td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Melanoma</b>
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</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin exam w/dermatologist</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Individualized based on family history</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Pancreatic</b>
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<br />
|
|
<b>cancer</b>
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</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In asymptomatic persons who meet criteria based on mutation status & family history, contrast-enhanced MRI/MRCP &/or EUS may be considered in a research setting to better delineate the risks & benefits of pancreatic cancer screening.</td><td headers="hd_h_brca1.T.recommended_surveillance_for_wom_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></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">EUS = endoscopic ultrasound; MRCP = magnetic resonance cholangiopancreatography</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="brca1.TF.4.1"><p class="no_margin">For women who have not elected to undergo prophylactic bilateral salpingo-oophorectomy: while some clinicians conduct annual transvaginal ultrasound and/or CA-125 concentration, these modalities have not been effective in detecting early-stage ovarian cancer, either in high-risk or in average-risk women.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1Trecommendedsurveillanceformen"><div id="brca1.T.recommended_surveillance_for_men" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Men with <i>BRCA1-</i> and <i>BRCA2-</i>Associated Hereditary Breast and Ovarian Cancer</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.recommended_surveillance_for_men/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.recommended_surveillance_for_men_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Breast cancer</b>
|
|
</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breast self-exam training</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At the time of identification of a <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Breast self-exam</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monthly beginning at age 35 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical breast exam</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 35 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Prostate cancer</b>
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</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serum PSA; digital rectal exam</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 40 yrs</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Melanoma</b>
|
|
</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin exam w/dermatologist</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Individualized based on family history</td></tr><tr><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Pancreatic</b>
|
|
<br />
|
|
<b>cancer</b>
|
|
</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In asymptomatic persons who meet criteria based on mutation status & family history, contrast-enhanced MRI/MRCP &/or EUS may be considered in a research setting to better delineate the risks & benefits of pancreatic cancer screening.</td><td headers="hd_h_brca1.T.recommended_surveillance_for_men_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></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">EUS = endoscopic ultrasound; MRCP = magnetic resonance cholangiopancreatography</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1molgenTA"><div id="brca1.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_brca1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_brca1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_brca1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_brca1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_brca1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_brca1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_brca1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/672" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
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<i>BRCA1</i>
|
|
</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=672" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">17q21<wbr style="display:inline-block"></wbr>​.31</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P38398" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast cancer type 1 susceptibility protein</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.LOVD.nl/BRCA1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA1 homepage - LOVD</a>
|
|
<br />
|
|
<a href="http://hci-exlovd.hci.utah.edu/home.php?select_db=BRCA1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Database of BRCA1 and BRCA2 sequence variants that have been clinically reclassified by a quantitative integrated evaluation</a>
|
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<br />
|
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<a href="https://research.nhgri.nih.gov/bic/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast Cancer Information Core (BRCA1)</a>
|
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<br />
|
|
<a href="https://lovd.nl/BRCA1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA1 @ ZAC-GGM</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BRCA1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA1</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=BRCA1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA1</a>
|
|
</td></tr><tr><td headers="hd_b_brca1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/675" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>BRCA2</i>
|
|
</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=675" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">13q13<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P51587" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast cancer type 2 susceptibility protein</a>
|
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</td><td headers="hd_b_brca1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.LOVD.nl/BRCA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA2 homepage - LOVD</a>
|
|
<br />
|
|
<a href="http://hci-exlovd.hci.utah.edu/home.php?select_db=BRCA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Database of BRCA1 and BRCA2 sequence variants that have been clinically reclassified using a quantitative integrated evaluation</a>
|
|
<br />
|
|
<a href="https://research.nhgri.nih.gov/bic/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Breast Cancer Information Core (BRCA2)</a>
|
|
<br />
|
|
<a href="http://www.rockefeller.edu/fanconi/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Fanconi Anaemia Mutation Database (FANCD1 - BRCA2)</a>
|
|
<br />
|
|
<a href="https://lovd.nl/BRCA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA2 @ ZAC-GGM</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BRCA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA2</a>
|
|
</td><td headers="hd_b_brca1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=BRCA2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BRCA2</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="brca1.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbrca1molgenTB"><div id="brca1.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer (<a href="/omim/113705,114480,600185,604370,612555,613347,614320" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/113705" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">113705</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BRCA1 DNA REPAIR-ASSOCIATED PROTEIN; BRCA1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/114480" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">114480</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BREAST CANCER</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/600185" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600185</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BRCA2 DNA REPAIR-ASSOCIATED PROTEIN; BRCA2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/604370" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604370</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; BROVCA1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/612555" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">612555</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; BROVCA2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613347" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613347</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PANCREATIC CANCER, SUSCEPTIBILITY TO, 2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/614320" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">614320</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PANCREATIC CANCER, SUSCEPTIBILITY TO, 4; PNCA4</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobbrca1Tbrca1andbrca2associatedheredi"><div id="brca1.T.brca1_and_brca2associated_heredi" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>BRCA1</i>- and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer: Notable Pathogenic Variants by Gene</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1247/table/brca1.T.brca1_and_brca2associated_heredi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__brca1.T.brca1_and_brca2associated_heredi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA1</i>
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</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_2" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_007294.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_007294<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_009225.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_009225<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.68_69delAG<br />(185delAG or 187delAG)</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu23ValfsTer17</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Ashkenazi Jews; accounts for 72% of pathogenic variants in this population <sup>2</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.115T>G</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys39Gly</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Inuit from Ammassalik; accounts for >95% of pathogenic variants in this population <sup>3</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.815_824dupAGCCATGTGG<br />(943ins10)</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Thr276AlafsTer14</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in those of West African ancestry <sup>4</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.5096G>A</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg1699Gln</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intermediate risk variant <sup>5</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.5266dupC<br />(5385insC or 5382insC)</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln1756ProfsTer74</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Ashkenazi Jews; accounts for 26% of pathogenic variants in this population <sup>2</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRCA2</i>
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</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000059.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000059<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000050.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000050<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.771_775delTCAAA (999del5)</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn257LysfsTer17</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Icelanders <sup>6</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.5073dupA</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Trp1692MetfsTer3</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Amish of Somerset County, Pennsylvania <sup>7</sup></td></tr><tr><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.5946delT<br />(6174delT)</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser1982ArgfsTer22</td><td headers="hd_h_brca1.T.brca1_and_brca2associated_heredi_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Ashkenazi Jews; accounts for 95% of pathogenic variants in this population <sup>2</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">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="brca1.TF.6.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="brca1.TF.6.2"><p class="no_margin"><a class="bibr" href="#brca1.REF.bahar.2001.440" rid="brca1.REF.bahar.2001.440">Bahar et al [2001]</a>, <a class="bibr" href="#brca1.REF.frank.2002.1480" rid="brca1.REF.frank.2002.1480">Frank et al [2002]</a>, <a class="bibr" href="#brca1.REF.phelan.2002.352" rid="brca1.REF.phelan.2002.352">Phelan et al [2002]</a>, <a class="bibr" href="#brca1.REF.ferla.2007" rid="brca1.REF.ferla.2007">Ferla et al [2007]</a>, <a class="bibr" href="#brca1.REF.cox.2018.1236" rid="brca1.REF.cox.2018.1236">Cox et al [2018]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="brca1.TF.6.3"><p class="no_margin"><a class="bibr" href="#brca1.REF.hansen.2009.69" rid="brca1.REF.hansen.2009.69">Hansen et al [2009]</a>, <a class="bibr" href="#brca1.REF.harboe.2009.413" rid="brca1.REF.harboe.2009.413">Harboe et al [2009]</a>, <a class="bibr" href="#brca1.REF.hansen.2010.259" rid="brca1.REF.hansen.2010.259">Hansen et al [2010]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="brca1.TF.6.4"><p class="no_margin">
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<a class="bibr" href="#brca1.REF.mefford.1999.575" rid="brca1.REF.mefford.1999.575">Mefford et al [1999]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="brca1.TF.6.5"><p class="no_margin">
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<a class="bibr" href="#brca1.REF.moghadasi.2018.15" rid="brca1.REF.moghadasi.2018.15">Moghadasi et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="brca1.TF.6.6"><p class="no_margin">
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<a class="bibr" href="#brca1.REF.rafnar.2004.2788" rid="brca1.REF.rafnar.2004.2788">Rafnar et al [2004]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="brca1.TF.6.7"><p class="no_margin">See <a href="/books/n/gene/founder_amish/?report=reader">Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Amish Population</a>.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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