{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Allen I"],"funding":["Cancer Research UK","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["651-661"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616773"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(6)"],"pubmed_abstract":["<h4>Purpose</h4>Second primary cancer (SPC) risks after breast cancer (BC) in <i>BRCA1/BRCA2</i> pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.<h4>Methods</h4>We followed 25,811 females and 480 males diagnosed with BC and tested for germline <i>BRCA1/BRCA2</i> PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.<h4>Results</h4>There were 1,840 <i>BRCA1</i> and 1,750 <i>BRCA2</i> female PV carriers. Compared with population incidences, <i>BRCA1</i> carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without <i>BRCA1/BRCA2</i> PVs on testing, <i>BRCA1</i> carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (<i>BRCA1</i> carriers), 12%/3.0%/6.2% (<i>BRCA2</i> carriers), and 3.6%/0.4%/4.9% (noncarriers). Male <i>BRCA2</i> carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.<h4>Conclusion</h4>Survivors of BC carrying <i>BRCA1</i> and <i>BRCA2</i> PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures."],"journal":["Journal of clinical oncology : official journal of the American Society of Clinical Oncology"],"pubmed_title":["Second Primary Cancer Risks After Breast Cancer in <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variant Carriers."],"pmcid":["PMC7616773"],"funding_grant_id":["NIHR203312","PPRPGM-Nov20\\100002","203924/Z/16/Z"],"pubmed_authors":["Loong L","Tischkowitz M","Antoniou AC","Santaniello F","Lavelle K","Luchtenborg M","Goel S","Knott C","Torr B","Vernon S","Huntley C","Hassan H","Morris E","Turnbull C","McRonald F","Pethick J","Bacon A","Garrett A","Allen I","Walburga Y","Jose S","Eccles D","Pharoah P","Rahman T","Wang YW","Allen S","Hardy S"],"additional_accession":[]},"is_claimable":false,"name":"Second Primary Cancer Risks After Breast Cancer in <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variant Carriers.","description":"<h4>Purpose</h4>Second primary cancer (SPC) risks after breast cancer (BC) in <i>BRCA1/BRCA2</i> pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.<h4>Methods</h4>We followed 25,811 females and 480 males diagnosed with BC and tested for germline <i>BRCA1/BRCA2</i> PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.<h4>Results</h4>There were 1,840 <i>BRCA1</i> and 1,750 <i>BRCA2</i> female PV carriers. Compared with population incidences, <i>BRCA1</i> carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without <i>BRCA1/BRCA2</i> PVs on testing, <i>BRCA1</i> carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (<i>BRCA1</i> carriers), 12%/3.0%/6.2% (<i>BRCA2</i> carriers), and 3.6%/0.4%/4.9% (noncarriers). Male <i>BRCA2</i> carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.<h4>Conclusion</h4>Survivors of BC carrying <i>BRCA1</i> and <i>BRCA2</i> PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2025-04-22T16:55:52.422Z","creation":"2025-04-06T01:58:40.504Z"},"accession":"S-EPMC7616773","cross_references":{"pubmed":["39475295"],"doi":["10.1200/JCO.24.01146"]}}