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</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">PALB2: Cancer Risks and Management (PDQ®): Health Professional Version</div><div class="j">PDQ Cancer Information Summaries [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 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class="fm-sec"><h1 id="_NBK609615_"><span class="title" itemprop="name">PALB2: Cancer Risks and Management (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contribs">PDQ Cancer Genetics Editorial Board.</p><p class="fm-aai"><a href="#_NBK609615_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000816204__2824">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the genetics of PALB2. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000816204__2825">This summary is reviewed regularly and updated as necessary by the PDQ Cancer Genetics Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000816204__2826"><h2 id="_CDR0000816204__2826_">Genetics</h2><p id="CDR0000816204__3751">The <i>PALB2</i> (Partner And Localizer of <i>BRCA2</i>) <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000045693/" class="def">gene</a> is located on <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000046470/" class="def">chromosome</a> 16p12.2. This gene interacts with both <i>BRCA2</i> and <i>BRCA1</i> to restore and maintain genomic stability via homologous recombination repair of <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000045671/" class="def">DNA</a> double-stranded breaks. Several studies have reported a high <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000339344/" class="def">penetrance</a> of breast cancer in women who carry <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a>. <i>PALB2</i> is now included on all breast cancer <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000763019/" class="def">multigene panel tests</a>. <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460154/" class="def">Germline</a>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000775789/" class="def">biallelic</a> loss-of-function of <i>PALB2</i> variants (also known as <i>FANCN</i>) lead to Fanconi anemia. Fanconi anemia is a syndrome that is associated with early developmental defects, bone marrow failure, and cancer <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000809370/" class="def">predisposition</a>.[<a class="bibr" href="#CDR0000816204_rl_2826_1" rid="CDR0000816204_rl_2826_1">1</a>]</p><div id="CDR0000816204_rl_2826"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2826_1">Wu S, Zhou J, Zhang K, et al.: Molecular Mechanisms of PALB2 Function and Its Role in Breast Cancer Management. Front Oncol 10: 301, 2020. [<a href="/pmc/articles/PMC7059202/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7059202</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32185139" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32185139</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2828"><h2 id="_CDR0000816204__2828_">Prevalence of <i>PALB2</i> Pathogenic Variants</h2><p id="CDR0000816204__2829">Several studies have reported prevalence rates of <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a>. These studies included case series, case-control studies, cohort studies, and commercial lab databases. There is considerable heterogeneity among these studies in terms of study design, populations studied, strength of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000302456/" class="def">family history,</a> sequencing techniques, and levels of coverage. Most of these studies included individuals who were referred for clinical genetic testing, and they are, therefore, are not representative of the general population. Prevalence rates in these studies ranged from 0.3% to 1.2%.[<a class="bibr" href="#CDR0000816204_rl_2828_1" rid="CDR0000816204_rl_2828_1">1</a>-<a class="bibr" href="#CDR0000816204_rl_2828_13" rid="CDR0000816204_rl_2828_13">13</a>] A meta-analysis analyzed data from 48 studies of women who were diagnosed with breast cancer and were referred for genetic testing. This meta-analysis found that prevalence of <i>PALB2</i> pathogenic variants was 0.9%, and the odds ratio for breast cancer was 4.87.[<a class="bibr" href="#CDR0000816204_rl_2828_14" rid="CDR0000816204_rl_2828_14">14</a>] Another study, which included only women with metastatic breast cancer, reported a <i>PALB2</i> prevalence of 1.8%.[<a class="bibr" href="#CDR0000816204_rl_2828_15" rid="CDR0000816204_rl_2828_15">15</a>] A study from a genetic testing lab found a <i>PALB2</i> prevalence of 0.36% in Caucasian women who were diagnosed with ovarian cancer.[<a class="bibr" href="#CDR0000816204_rl_2828_3" rid="CDR0000816204_rl_2828_3">3</a>] Despite the variability in study design and study populations, prevalence rates for <i>PALB2</i> pathogenic variants were very similar. </p><p id="CDR0000816204__3752"><i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783962/" class="def">founder pathogenic variants</a> have been described in Finnish, Polish, Canadian, Russian, Argentinian, Greek, Italian, Australian, and Hispanic populations.</p><div id="CDR0000816204_rl_2828"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2828_1">Norquist BM, Harrell MI, Brady MF, et al.: Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol 2 (4): 482-90, 2016. [<a href="/pmc/articles/PMC4845939/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4845939</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26720728" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26720728</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_2">Pritzlaff M, Summerour P, McFarland R, et al.: Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. Breast Cancer Res Treat 161 (3): 575-586, 2017. [<a href="/pmc/articles/PMC5241330/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5241330</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28008555" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28008555</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_3">Lilyquist J, LaDuca H, Polley E, et al.: Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. Gynecol Oncol 147 (2): 375-380, 2017. [<a href="/pmc/articles/PMC5801741/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5801741</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28888541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28888541</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_4">Weitzel JN, Neuhausen SL, Adamson A, et al.: Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer. Cancer 125 (16): 2829-2836, 2019. [<a href="/pmc/articles/PMC7376605/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7376605</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31206626" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31206626</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_5">Rizzolo P, Zelli V, Silvestri V, et al.: Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy. Int J Cancer 145 (2): 390-400, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30613976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30613976</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_6">Deng M, Chen HH, Zhu X, et al.: Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China. Int J Cancer 145 (6): 1517-1528, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30720863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30720863</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_7">Fan X, Wynn J, Shang N, et al.: Penetrance of Breast Cancer Susceptibility Genes From the eMERGE III Network. JNCI Cancer Spectr 5 (4): , 2021. [<a href="/pmc/articles/PMC8346699/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8346699</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34377931" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34377931</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_8">Fasching PA, Yadav S, Hu C, et al.: Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis. J Clin Oncol 39 (15): 1619-1630, 2021. [<a href="/pmc/articles/PMC8274805/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8274805</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33780288" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33780288</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_9">Daly MB, Rosenthal E, Cummings S, et al.: The association between age at breast cancer diagnosis and prevalence of pathogenic variants. Breast Cancer Res Treat 199 (3): 617-626, 2023. [<a href="/pmc/articles/PMC10175307/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10175307</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37084156" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37084156</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_10">Kurian AW, Hughes E, Handorf EA, et al.: Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women. JCO Precis Oncol 1: 1-12, 2017. [<a href="https://pubmed.ncbi.nlm.nih.gov/35172496" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35172496</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_11">Kotsopoulos J, Hathaway CA, Narod SA, et al.: Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts. Cancer Epidemiol Biomarkers Prev 32 (10): 1402-1410, 2023. [<a href="/pmc/articles/PMC10592229/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10592229</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37493628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37493628</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_12">Bucalo A, Conti G, Valentini V, et al.: Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study. Eur J Cancer 188: 183-191, 2023. [<a href="https://pubmed.ncbi.nlm.nih.gov/37262986" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37262986</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_13">Morra A, Mavaddat N, Muranen TA, et al.: The impact of coding germline variants on contralateral breast cancer risk and survival. Am J Hum Genet 110 (3): 475-486, 2023. [<a href="/pmc/articles/PMC10027471/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10027471</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36827971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36827971</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_14">Suszynska M, Klonowska K, Jasinska AJ, et al.: Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes. Gynecol Oncol 153 (2): 452-462, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30733081" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30733081</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2828_15">Rolfes M, Borde J, Möllenhoff K, et al.: Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancers (Basel) 14 (13): , 2022. [<a href="/pmc/articles/PMC9265404/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9265404</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35805063" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35805063</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2830"><h2 id="_CDR0000816204__2830_"><i>PALB2</i> Cancer Risks, Spectrum, and Characteristics</h2><div id="CDR0000816204__2832"><h3>Female Breast Cancer Risk Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2833">The association between <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a> and female breast cancer was first reported in 2007.[<a class="bibr" href="#CDR0000816204_rl_2830_1" rid="CDR0000816204_rl_2830_1">1</a>] After the publication of several small studies, a 2014 report by the <i>PALB2</i> Interest Group (PALB2-IG) (from 14 international research centers, involving 154 families with loss-of-function <i>PALB2</i> pathogenic variants) confirmed that the risk range for female breast cancer in <i>PALB2</i> overlapped with that of <i>BRCA2</i>.[<a class="bibr" href="#CDR0000816204_rl_2830_2" rid="CDR0000816204_rl_2830_2">2</a>] Analysis of 311 women from these 154 families found that by age 70, absolute risk of female breast cancer was 33% (95% confidence interval [CI], 24%‒44%) for those without <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000302456/" class="def">family histories</a> of breast cancer and 58% (95% CI, 50%‒66%) for those with two or more <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460150/" class="def">first-degree relatives</a> (FDRs) with early-onset breast cancer. A cohort effect was also observed, in which breast cancer risk was significantly higher in women from more recent birth cohorts. Thirty percent of women with available hormone receptor and human epidermal growth factor receptor 2 (HER2) statuses had <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000639916/" class="def">triple-negative breast cancers</a>.</p><p id="CDR0000816204__3753">In 2019, this study was updated and expanded to include 8,830 women in 524 families from 44 study centers in 21 countries.[<a class="bibr" href="#CDR0000816204_rl_2830_3" rid="CDR0000816204_rl_2830_3">3</a>] Families included at least one member with a <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variant.</a> Individuals with known <i>BRCA1/2</i> pathogenic variants were excluded. The absolute risk of breast cancer was 16.9% (95% CI, 13.3%‒21.3%) by age 50 years and 52.8% (95% CI, 43.7%‒62.7%) by age 80 years. Like in the earlier study, both family history and birth cohort were significantly related to risk.</p><p id="CDR0000816204__3754">To avoid bias of studying only women with increased breast cancer risk, researchers sequenced <i>PALB2</i> in 16,501 unselected <i>BRCA1/2</i>-negative breast cancer patients from 10 provinces in China.[<a class="bibr" href="#CDR0000816204_rl_2830_4" rid="CDR0000816204_rl_2830_4">4</a>] This study found a <i>PALB2</i> pathogenic <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000776887/" class="def">variant</a> prevalence of 0.97%, which is similar to prevalence estimates reported in other studies. The overall odds ratio (OR) for breast cancer risk in women with <i>PALB2</i> pathogenic variants was 5.23 (95% CI, 2.84‒9.65). However, there was a significant association between breast cancer risk and age, with an OR of 10.09 (95% CI, 3.95‒25.70) for women age 30 years or younger and 5.06 (95% CI, 2.74‒9.43) for women older than 30 years. <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460132/" class="def">carriers</a> were more likely to have family histories of breast and/or ovarian cancer (20.63% vs.7.96% in noncarriers). These individuals were more likely to have larger tumors and positive axillary lymph nodes than controls. The Breast Cancer Association Consortium (BCAC) sequenced 34 suspected breast cancer susceptibility <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000045693/" class="def">genes</a> in 60,466 women with invasive breast cancer and 53,461 controls to refine estimates for breast cancer risk.[<a class="bibr" href="#CDR0000816204_rl_2830_5" rid="CDR0000816204_rl_2830_5">5</a>] The OR for breast cancer risk in women with <i>PALB2</i> pathogenic variants was 5.02 (95% CI, 3.73‒6.76). The OR was higher for estrogen receptor (ER)‒negative breast cancer. </p></div><div id="CDR0000816204__2834"><h3>Contralateral Breast Cancer Risk Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2835">Data on contralateral breast cancer (CBC) risk in <i>PALB2</i> carriers are limited. Although there are limited data, both the CARRIERS Consortium and the BCAC have published similar findings.[<a class="bibr" href="#CDR0000816204_rl_2830_6" rid="CDR0000816204_rl_2830_6">6</a>,<a class="bibr" href="#CDR0000816204_rl_2830_7" rid="CDR0000816204_rl_2830_7">7</a>] The CARRIERS study included data from ten prospective studies of 15,104 women with <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000660739/" class="def">genotype</a> and <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460203/" class="def">phenotype</a> data.[<a class="bibr" href="#CDR0000816204_rl_2830_6" rid="CDR0000816204_rl_2830_6">6</a>] The overall hazard ratio (HR) for CBC in <i>PALB2</i> carriers was 2.9 (95% CI, 1.4‒6.4). CBC risk was seen primarily in women with ER-negative disease. The HR for CBC in <i>PALB2</i> carriers with ER-negative disease was 3.7 (95% CI, 1.5‒9.0). The 10-year cumulative risk of CBC was 7.9% overall and 19.7% in women with ER-negative breast cancer. CBC risk was significantly higher in African American women with ER-negative breast cancer, in whom the HR was 4.8 (95% CI, 1.4–16.8). CBC risk in this population was observed predominantly in women who were premenopausal when they were diagnosed with breast cancer. The BCAC report included 30,628 women from 34 studies.[<a class="bibr" href="#CDR0000816204_rl_2830_7" rid="CDR0000816204_rl_2830_7">7</a>] The HR for CBC in women with <i>PALB2</i> pathogenic variants was 2.67 (95% CI, 1.35‒5.35). <i>PALB2</i> carriers had poorer survival when compared with noncarriers, but this association was not significant when it was adjusted to include tumor characteristics.</p></div><div id="CDR0000816204__2836"><h3>Male Breast Cancer Risk Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2837">Risk of male breast cancer in the general population is 0.1%. However, this cancer clusters in families with breast cancer cases. While there are few studies on pathogenic variants identified in men diagnosed with breast cancer, several reports have detected <i>PALB2</i> pathogenic variants in this population. Data on 708 men with breast cancer who underwent testing at one genetic testing lab found an OR of 6.6 (95% CI, 1.7‒21.1) for breast cancer in men with a <i>PALB2</i> pathogenic variant, although the number of individuals with <i>PALB2</i> pathogenic variants in this study was small.[<a class="bibr" href="#CDR0000816204_rl_2830_8" rid="CDR0000816204_rl_2830_8">8</a>] A large case-control study from Italy that included 767 <i>BRCA1/2</i>-negative men with breast cancer found an OR of 7.28 (95% CI, 1.17‒45.42) for male breast cancer in men with <i>PALB2</i> pathogenic variants.[<a class="bibr" href="#CDR0000816204_rl_2830_9" rid="CDR0000816204_rl_2830_9">9</a>] Like in <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000339347/" class="def">sporadic male breast cancer</a>, most tumors in men with non-<i>BRCA1/2</i> pathogenic variants were invasive ductal carcinomas that were ER-positive, progesterone receptor‒positive, and HER2-negative. Similarly, the PALB2-IG study of 524 families with <i>PALB2</i> pathogenic variants reported a relative risk (RR) of 7.34 (95% CI, 1.28‒42.19) for male breast cancer.[<a class="bibr" href="#CDR0000816204_rl_2830_3" rid="CDR0000816204_rl_2830_3">3</a>] Despite small numbers, estimates of male breast cancer risk associated with <i>PALB2</i> are consistent across studies. <i>PALB2</i> is emerging as the second-most commonly mutated gene in male breast cancer, after <i>BRCA2</i>.</p></div><div id="CDR0000816204__2838"><h3>Pancreatic Cancer Risk Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2839">A study first reported a <i>PALB2</i> pathogenic variant in an individual with <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460148/" class="def">familial</a> pancreatic cancer in 2009 using exome sequencing.[<a class="bibr" href="#CDR0000816204_rl_2830_10" rid="CDR0000816204_rl_2830_10">10</a>] In subsequent studies of individuals with exocrine pancreatic cancer, <i>PALB2</i> pathogenic variants were found in 2% to 4% of participants.[<a class="bibr" href="#CDR0000816204_rl_2830_11" rid="CDR0000816204_rl_2830_11">11</a>,<a class="bibr" href="#CDR0000816204_rl_2830_12" rid="CDR0000816204_rl_2830_12">12</a>] In the PALB2-IG study (with 524 <i>PALB2</i> families), the RR was 2.4 (95% CI, 1.24‒4.50) for pancreatic cancer when <i>PALB2</i> pathogenic variants were present.[<a class="bibr" href="#CDR0000816204_rl_2830_3" rid="CDR0000816204_rl_2830_3">3</a>] In individuals with <i>PALB2</i> pathogenic variants, the absolute lifetime risk of pancreatic cancer is estimated to be between 5% and 10%.</p></div><div id="CDR0000816204__2840"><h3>Ovarian Cancer Risk Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2841">Although data on the association between <i>PALB2</i> pathogenic variants and ovarian cancer are mixed, there is growing acknowledgement that ovarian cancer risk may be moderately increased in <i>PALB2</i> carriers. Ovarian cancer risk is further increased in women who are diagnosed with ovarian cancer at young ages and in those with family histories of breast/ovarian cancers.</p><p id="CDR0000816204__3757">A University of Washington study ascertained the frequency of <i>PALB2</i> pathogenic variants in patients with ovarian cancer.[<a class="bibr" href="#CDR0000816204_rl_2830_13" rid="CDR0000816204_rl_2830_13">13</a>] Patients were unselected for age/family history and were enrolled through a university biobank and two Gynecologic Oncology Group (GOG) clinical trials for advanced ovarian cancer. The OR for ovarian cancer was 10.2 (95% CI, 2.2‒47.0). A similar study on the frequency of pathogenic variants from <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000763019/" class="def">multigene panel testing</a> in a series of clinically ascertained ovarian cancer cases (participants were referred to one genetic testing lab) found a standardized risk ratio of 3.08 (95% CI, 1.93‒4.67) for <i>PALB2</i>.[<a class="bibr" href="#CDR0000816204_rl_2830_14" rid="CDR0000816204_rl_2830_14">14</a>] The authors speculated that this association was driven by a strong association between <i>PALB2</i> and breast cancer risk, since participants were 3.5-times more likely to have personal or family histories of breast cancer when compared with reference controls. Similar data from a different genetic testing lab reported an OR of 1.60 for ovarian cancer (95% CI, 0.98‒2.60), which did not meet statistical significance.[<a class="bibr" href="#CDR0000816204_rl_2830_15" rid="CDR0000816204_rl_2830_15">15</a>] Researchers sequenced the coding regions of 54 candidate genes in 6,385 women with invasive ovarian cancer and 6,115 controls with broad European ancestry from 19 studies (mostly case-control studies).[<a class="bibr" href="#CDR0000816204_rl_2830_16" rid="CDR0000816204_rl_2830_16">16</a>] This study found that <i>PALB2</i> pathogenic variants were associated with a moderate risk of high-grade serous ovarian cancer (OR, 2.60; 95% CI, 1.45‒4.64; <i>P</i> = .0013). The cumulative absolute risk of ovarian cancer in <i>PALB2</i> carriers by age 80 years was 3.2% (95% CI, 1.8%‒5.7%). Similarly, the PALB2-IG study found an estimated RR of 2.91 (95% CI, 1.40‒6.04) for ovarian cancer in <i>PALB2</i> carriers and an absolute lifetime ovarian cancer risk of approximately 5%.[<a class="bibr" href="#CDR0000816204_rl_2830_3" rid="CDR0000816204_rl_2830_3">3</a>] The aforementioned meta-analysis of 48 studies found an OR of 2.13 for ovarian cancer.[<a class="bibr" href="#CDR0000816204_rl_2830_17" rid="CDR0000816204_rl_2830_17">17</a>]</p></div><div id="CDR0000816204__2842"><h3>Other Cancer Risks Associated with <i>PALB2</i> Pathogenic Variants</h3><p id="CDR0000816204__2843"><i>PALB2</i> pathogenic variants have been described in colorectal, gastric, prostate, and other cancers.[<a class="bibr" href="#CDR0000816204_rl_2830_3" rid="CDR0000816204_rl_2830_3">3</a>] However, <i>PALB2</i>'s contribution to risk in these cancer types has not yet been confirmed. For more information about research on <i>PALB2</i> and gastric cancer risk, see the <a href="/books/n/pdqcis/CDR0000802835/?report=reader#CDR0000802835__3805">Other Genes Associated With Gastric Cancer</a> section in Genetics of Gastric Cancer.</p></div><div id="CDR0000816204_rl_2830"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2830_1">Rahman N, Seal S, Thompson D, et al.: PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39 (2): 165-7, 2007. [<a href="/pmc/articles/PMC2871593/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2871593</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17200668" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17200668</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_2">Antoniou AC, Casadei S, Heikkinen T, et al.: Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371 (6): 497-506, 2014. [<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></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_3">Yang X, Leslie G, Doroszuk A, et al.: Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol 38 (7): 674-685, 2020. [<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></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_4">Zhou J, Wang H, Fu F, et al.: Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. Cancer 126 (14): 3202-3208, 2020. [<a href="/pmc/articles/PMC7384117/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7384117</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32339256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32339256</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_5">Dorling L, Carvalho S, Allen J, et al.: Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med 384 (5): 428-439, 2021. [<a href="/pmc/articles/PMC7611105/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7611105</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33471991" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33471991</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_6">Yadav S, Boddicker NJ, Na J, et al.: Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. J Clin Oncol 41 (9): 1703-1713, 2023. [<a href="/pmc/articles/PMC10022863/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10022863</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36623243" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36623243</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_7">Morra A, Mavaddat N, Muranen TA, et al.: The impact of coding germline variants on contralateral breast cancer risk and survival. Am J Hum Genet 110 (3): 475-486, 2023. [<a href="/pmc/articles/PMC10027471/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10027471</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36827971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36827971</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_8">Pritzlaff M, Summerour P, McFarland R, et al.: Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. Breast Cancer Res Treat 161 (3): 575-586, 2017. [<a href="/pmc/articles/PMC5241330/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5241330</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28008555" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28008555</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_9">Bucalo A, Conti G, Valentini V, et al.: Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study. Eur J Cancer 188: 183-191, 2023. [<a href="https://pubmed.ncbi.nlm.nih.gov/37262986" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37262986</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_10">Jones S, Hruban RH, Kamiyama M, et al.: Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324 (5924): 217, 2009. [<a href="/pmc/articles/PMC2684332/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2684332</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19264984" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19264984</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_11">Slater EP, Langer P, Niemczyk E, et al.: PALB2 mutations in European familial pancreatic cancer families. Clin Genet 78 (5): 490-4, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20412113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20412113</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_12">Hofstatter EW, Domchek SM, Miron A, et al.: PALB2 mutations in familial breast and pancreatic cancer. Fam Cancer 10 (2): 225-31, 2011. [<a href="/pmc/articles/PMC3836668/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3836668</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21365267" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21365267</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_13">Norquist BM, Harrell MI, Brady MF, et al.: Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol 2 (4): 482-90, 2016. [<a href="/pmc/articles/PMC4845939/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4845939</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26720728" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26720728</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_14">Lilyquist J, LaDuca H, Polley E, et al.: Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. Gynecol Oncol 147 (2): 375-380, 2017. [<a href="/pmc/articles/PMC5801741/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5801741</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28888541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28888541</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_15">Kurian AW, Hughes E, Handorf E: Association of ovarian cancer (OC) risk with mutations detected by multiple-gene germline sequencing in 95,561 women. [Abstract] J Clin Oncol 34 (Suppl 15): A-5510, 2016. <a href="https://ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.5510" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Also available online</a>. Last accessed November 7, 2024.</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_16">Song H, Dicks EM, Tyrer J, et al.: Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer. J Med Genet 58 (5): 305-313, 2021. [<a href="/pmc/articles/PMC8086250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8086250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32546565" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32546565</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2830_17">Suszynska M, Klonowska K, Jasinska AJ, et al.: Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes. Gynecol Oncol 153 (2): 452-462, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30733081" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30733081</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2844"><h2 id="_CDR0000816204__2844_">Cancer Surveillance and Risk Management in <i>PALB2</i> Carriers</h2><p id="CDR0000816204__2845">The National Comprehensive Cancer Network (NCCN) recommends breast cancer <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000046171/" class="def">screening</a> with annual mammogram and breast magnetic resonance imaging (MRI) with contrast starting at age 30 years in women with <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a>.[<a class="bibr" href="#CDR0000816204_rl_2844_1" rid="CDR0000816204_rl_2844_1">1</a>] Given the increased contralateral breast cancer risk seen in premenopausal women with <i>PALB2</i> pathogenic variants, MRI screening can also be conducted following a primary breast cancer. However, MRI screening may be of little benefit after age 65 years in this population. Risk-reducing mastectomy can be considered, based on the individual’s <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000302456/" class="def">family history</a>. In men with <i>PALB2</i> pathogenic variants, breast cancer screening with annual mammogram may be considered starting at age 50 years or 10 years earlier than the youngest breast cancer diagnosis in the family. Risk-reducing salpingo-oophorectomy may be considered for women starting at age 45 to 50 years. Because family history can impact ovarian cancer risk in <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460132/" class="def">carriers</a>, individualized <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460214/" class="def">risk assessment</a> is encouraged.[<a class="bibr" href="#CDR0000816204_rl_2844_2" rid="CDR0000816204_rl_2844_2">2</a>] Protocols for pancreatic cancer screening vary but mainly include contrast-enhanced MRI/magnetic resonance cholangiopancreatography and endoscopic ultrasound starting at age 50 years or 10 years before the earliest pancreatic cancer diagnosis in the family.[<a class="bibr" href="#CDR0000816204_rl_2844_1" rid="CDR0000816204_rl_2844_1">1</a>] Historically, professional organizations have recommended pancreatic cancer screening only when a family history of pancreatic cancer is present. However, recommendations conflict across professional organizations when a family history of pancreatic cancer is absent. Ongoing discussions with health care providers is encouraged, given the evolving data. </p><div id="CDR0000816204_rl_2844"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2844_1">National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Version 1.2025 . Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2025. <a href="https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online with free registration.</a> Last accessed October 30, 2024. [<a href="https://pubmed.ncbi.nlm.nih.gov/33406487" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33406487</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2844_2">Hanson H, Kulkarni A, Loong L, et al.: UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2. J Med Genet 60 (5): 417-429, 2023. [<a href="/pmc/articles/PMC10176381/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10176381</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36411032" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36411032</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2846"><h2 id="_CDR0000816204__2846_">Prognosis in <i>PALB2</i> Carriers</h2><div id="CDR0000816204__2848"><h3>Breast Cancer Prognosis in <i>PALB2</i> Carriers</h3><p id="CDR0000816204__2849">A prospective cohort study of 12,529 women with invasive breast cancer in Poland first reported an excess of <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000639916/" class="def">triple-negative breast cancer</a> (TNBC) in <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460132/" class="def">carriers</a> when compared with noncarriers.[<a class="bibr" href="#CDR0000816204_rl_2846_1" rid="CDR0000816204_rl_2846_1">1</a>] In this study, the hazard ratio (HR) for death associated with <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a> was 2.19 (95% confidence interval, 1.59‒3.02). However, this HR pertained to women with tumors larger than 2 cm. In a study of 16,501 unselected <i>BRCA1/2</i>-negative breast cancer patients from China, <i>PALB2</i> carriers were significantly more likely to have TNBCs than noncarriers (22.83% vs. 13.56%, respectively).[<a class="bibr" href="#CDR0000816204_rl_2846_2" rid="CDR0000816204_rl_2846_2">2</a>] <i>PALB2</i> carriers had larger tumors, more positive axillary lymph nodes, and more contralateral breast cancers. Other studies reported that <i>PALB2</i> carriers had TNBC rates ranging from 30% to 40%.[<a class="bibr" href="#CDR0000816204_rl_2846_3" rid="CDR0000816204_rl_2846_3">3</a>] A large population-based study in China observed a significantly shorter overall survival in <i>PALB2</i> carriers with breast cancer than in noncarriers.[<a class="bibr" href="#CDR0000816204_rl_2846_4" rid="CDR0000816204_rl_2846_4">4</a>] </p></div><div id="CDR0000816204_rl_2846"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2846_1">Cybulski C, Kluźniak W, Huzarski T, et al.: Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis. Lancet Oncol 16 (6): 638-44, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25959805" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25959805</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2846_2">Zhou J, Wang H, Fu F, et al.: Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. Cancer 126 (14): 3202-3208, 2020. [<a href="/pmc/articles/PMC7384117/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7384117</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32339256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32339256</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2846_3">Antoniou AC, Casadei S, Heikkinen T, et al.: Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371 (6): 497-506, 2014. [<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></li><li><div class="bk_ref" id="CDR0000816204_rl_2846_4">Deng M, Chen HH, Zhu X, et al.: Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China. Int J Cancer 145 (6): 1517-1528, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30720863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30720863</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2852"><h2 id="_CDR0000816204__2852_">Cancer Treatment in <i>PALB2</i> Carriers</h2><p id="CDR0000816204__2853">Because <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a> are relatively rare, data on treatment are scarce. However, <i>PALB2</i> interacts with <i>BRCA1/2</i> to maintain the integrity of the homologous recombination pathway. Therefore, tumors that lack <i>PALB2</i> activity may respond similarly to drugs that are effective in <i>BRCA1</i>/<i>2</i>-mutated tumors. A number of studies have reported that solid tumors with <i>PALB2</i> pathogenic variants had increased <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000322883/" class="def">sensitivity</a> to platinum agents.[<a class="bibr" href="#CDR0000816204_rl_2852_1" rid="CDR0000816204_rl_2852_1">1</a>] Several phase II trials have suggested that poly (ADP-ribose) polymerase (PARP) inhibitors may exhibit activity in patients with <i>PALB2</i> pathogenic variants. Although some data show that tumors with <i>PALB2</i> pathogenic variants have high tumor mutational burdens and tumor neoantigen burdens, data on the activity of immunosuppressive therapies are lacking. Several studies are examining the efficacy of using PARP inhibitors with other agents in <i>PALB2</i>-mutated breast tumors, ovarian tumors, and other solid tumors.[<a class="bibr" href="#CDR0000816204_rl_2852_2" rid="CDR0000816204_rl_2852_2">2</a>]</p><div id="CDR0000816204_rl_2852"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000816204_rl_2852_1">Tischkowitz M, Balmaña J, Foulkes WD, et al.: Management of individuals with germline variants in PALB2: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 23 (8): 1416-1423, 2021. [<a href="https://pubmed.ncbi.nlm.nih.gov/33976419" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33976419</span></a>]</div></li><li><div class="bk_ref" id="CDR0000816204_rl_2852_2">Toss A, Ponzoni O, Riccò B, et al.: Management of PALB2-associated breast cancer: A literature review and case report. Clin Case Rep 11 (8): e7747, 2023. [<a href="/pmc/articles/PMC10444947/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10444947</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37621724" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37621724</span></a>]</div></li></ol></div></div><div id="CDR0000816204__2854"><h2 id="_CDR0000816204__2854_"><i>PALB2</i> Summary</h2><p id="CDR0000816204__2855">Although rare, <i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000783960/" class="def">pathogenic variants</a> significantly increase the risk of breast, pancreatic, and ovarian cancers. <i>PALB2</i> pathogenic variant prevalence rates in published studies range from 0.3% to 1.8% and have been found in countries across the globe. Rates of breast cancer in individuals with <i>PALB2</i> pathogenic variants are similar to those associated with <i>BRCA2</i>. However, individuals with <i>PALB2</i> and <i>BRCA2</i> pathogenic variants have higher rates of <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000639916/" class="def">triple-negative breast cancer</a>. <i>PALB2</i> pathogenic variants are also associated with increased risks of contralateral breast cancer and male breast cancer.</p><p id="CDR0000816204__3755"><i>PALB2</i>
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<a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000460132/" class="def">carriers</a> have significantly increased risk to develop pancreatic cancer. Although there are conflicting data about <i>PALB2</i>’s role in ovarian cancer, there is also growing evidence that <i>PALB2</i> pathogenic variants confer moderately increased ovarian cancer risk.</p><p id="CDR0000816204__3756"><a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000496506/" class="def">Surveillance</a> and risk management recommendations are mainly based on data from <i>BRCA</i> trials. There is increased interest and activity in clinical trials to include individuals who carry <i>PALB2</i> pathogenic <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000776887/" class="def">variants</a>. </p></div><div id="CDR0000816204__2856"><h2 id="_CDR0000816204__2856_">Latest Updates to This PDQ Summary (11/20/2024)</h2><p id="CDR0000816204__2857">The PDQ cancer information summaries are reviewed regularly
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and updated as new information becomes available. This section
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describes the latest changes made to this summary as of the
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date above.</p><p id="CDR0000816204__3750">This is a new summary.</p><p id="CDR0000816204__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/genetics" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Cancer Genetics Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000816204__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000816204__AboutThis_1"><h2 id="_CDR0000816204__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000816204__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000816204__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about PALB2. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000816204__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000816204__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/genetics" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Cancer Genetics Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000816204__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000816204__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000816204__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewers for PALB2 are:</p><ul><li class="half_rhythm"><div>Doreen Agnese, MD (The Ohio State University)</div></li><li class="half_rhythm"><div>Ilana Cass, MD (Dartmouth-Hitchcock Medical Center)</div></li><li class="half_rhythm"><div>Lee-may Chen, MD (UCSF Helen Diller Family Comprehensive Cancer Center)</div></li><li class="half_rhythm"><div>Mary B. Daly, MD, PhD (Fox Chase Cancer Center)</div></li><li class="half_rhythm"><div>Megan Frone, MS, CGC (National Cancer Institute)</div></li><li class="half_rhythm"><div>Jessica Hatton , MS, CGC (National Cancer Institute)</div></li><li class="half_rhythm"><div>Joanne Kotsopoulos, PhD (University of Toronto and Women's College Hospital)</div></li><li class="half_rhythm"><div>Tuya Pal, MD, FACMG, FCCMG (Vanderbilt-Ingram Cancer Center)</div></li><li class="half_rhythm"><div>Padma Sheila Rajagopal, MD, MPH, MSC (National Cancer Institute)</div></li></ul><p id="CDR0000816204__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000816204__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000816204__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Cancer Genetics Editorial Board uses a <a href="/books/n/pdqcis/CDR0000685387/?report=reader">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000816204__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000816204__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000816204__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000816204__AboutThis_15">PDQ® Cancer Genetics Editorial Board. PDQ PALB2. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/publications/pdq/information-summaries/genetics/palb2-hp-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/publications/pdq/information-summaries/genetics/palb2-hp-pdq</a>. Accessed <MM/DD/YYYY>. </p><p id="CDR0000816204__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000816204__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000816204__AboutThis_19">The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000816204__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000816204__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div><div class="fm-sec"><h2 id="_NBK609615_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">PDQ Cancer Genetics Editorial Board</span>.</p><h3>Publication History</h3><p class="small">Published online: November 20, 2024.</p><p class="small">Created: <span itemprop="datePublished">November 20, 2024</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>PDQ Cancer Genetics Editorial Board. PALB2: Cancer Risks and Management (PDQ®): Health Professional Version. 2024 Nov 20. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></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></div></div>
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