{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:48:05Z","timestamp":1784886485110,"version":"3.55.0"},"reference-count":33,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,2,20]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Second primary cancer (SPC) risks after breast cancer (BC) in\n              <jats:italic>BRCA1\/BRCA2<\/jats:italic>\n              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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              We followed 25,811 females and 480 males diagnosed with BC and tested for germline\n              <jats:italic>BRCA1\/BRCA2<\/jats:italic>\n              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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              There were 1,840\n              <jats:italic>BRCA1<\/jats:italic>\n              and 1,750\n              <jats:italic>BRCA2<\/jats:italic>\n              female PV carriers. Compared with population incidences,\n              <jats:italic>BRCA1<\/jats:italic>\n              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.\n              <jats:italic>BRCA2<\/jats:italic>\n              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\n              <jats:italic>BRCA1\/BRCA2<\/jats:italic>\n              PVs on testing,\n              <jats:italic>BRCA1<\/jats:italic>\n              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.\n              <jats:italic>BRCA2<\/jats:italic>\n              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% (\n              <jats:italic>BRCA1<\/jats:italic>\n              carriers), 12%\/3.0%\/6.2% (\n              <jats:italic>BRCA2<\/jats:italic>\n              carriers), and 3.6%\/0.4%\/4.9% (noncarriers). Male\n              <jats:italic>BRCA2<\/jats:italic>\n              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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              Survivors of BC carrying\n              <jats:italic>BRCA1<\/jats:italic>\n              and\n              <jats:italic>BRCA2<\/jats:italic>\n              PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco.24.01146","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T19:59:10Z","timestamp":1730231950000},"page":"651-661","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Second Primary Cancer Risks After Breast Cancer in\n            <i>BRCA1<\/i>\n            and\n            <i>BRCA2<\/i>\n            Pathogenic Variant Carriers"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4640-3617","authenticated-orcid":true,"given":"Isaac","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom"},{"name":"National Disease Registration Service, National Health Service England, London, 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