{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:44:50Z","timestamp":1788335090760,"version":"build-2803163510"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Risk-reducing bilateral salpingo-oophorectomy is recommended to substantially lower ovarian cancer risk in women carrying\n BRCA1<\/jats:italic>\n or\n BRCA2<\/jats:italic>\n pathogenic variant (PV). The use of hormone replacement therapy (HRT) after risk-reducing bilateral oophorectomy (RRBO), although generally recommended, remains debated due to concerns about its possible role in breast cancer (BC) risk.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess the possible association between HRT use and BC incidence after RRBO in women harboring a limited range of germline\n BRCA<\/jats:italic>\n PVs.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This retrospective multicenter cohort study was conducted at 3 medical centers, including both referral and primary care facilities, in Israel. Cancer-free women (aged \u226518 years) with\n BRCA1<\/jats:italic>\n PV or\n BRCA2<\/jats:italic>\n PV, with no prior mastectomy, who underwent RRBO between January 1, 2000, and December 31, 2024, and who had at least 1 year of follow-up after RRBO were included.\n <\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n HRT use after RRBO.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n First diagnosis or incidence of invasive BC. BC diagnoses were ascertained through pathology reports and diagnostic codes used in the electronic health records; some were confirmed via participant interviews. HRT use was assessed through medical records, pharmacy dispensing data, clinic visits, and telephone interviews. Cox proportional hazards regression models, with HRT modeled as a time-varying covariate, evaluated the associations with BC risk while adjusting for potential confounders.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 919 women (mean [SD] age at RRBO, 47.6 [8.9] years) were included, of whom 496 had\n BRCA1<\/jats:italic>\n PV and 423 had\n BRCA2<\/jats:italic>\n PV. During a mean (SD) follow-up of 8.8 (6.2) years, 144 women (16%) were diagnosed with invasive BC. Overall, 381 participants (42%) had ever used and 538 (58%) had never used HRT following RRBO. Ever use of HRT was not associated with increased BC risk (combined estrogen-progestin: hazard ratio [HR], 1.06 [95% CI, 0.67-1.68]; estrogen only: HR, 0.89 [95% CI, 0.48-1.63]). In duration of use analyses, each year of estrogen-only HRT was associated with a reduction in BC risk overall (HR, 0.90; 95% CI, 0.81-0.99) and a reduction among participants with\n BRCA1<\/jats:italic>\n PV (HR, 0.87; 95% CI, 0.77-0.98).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this cohort study of women with\n BRCA<\/jats:italic>\n PV who received HRT after RRBO, estrogen-only HRT was not associated with an increased risk of BC and was associated with a lower risk of BC among women with\n BRCA1<\/jats:italic>\n PV. Combined estrogen-progestin HRT was not associated with BC risk modification.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.5648","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:00:39Z","timestamp":1775660439000},"page":"e265648","source":"Crossref","is-referenced-by-count":1,"title":["Hormone Therapy After Oophorectomy and Breast Cancer Risk in Women With\n BRCA<\/i>\n Pathogenic Variant"],"prefix":"10.1001","volume":"9","author":[{"given":"Shira","family":"Regev-Sadeh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel"},{"name":"School of Public Health, Gray Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel"},{"name":"Ruth and Bruch Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 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Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunit","family":"Armon","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Department of Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalfi","family":"Qarawani","sequence":"additional","affiliation":[{"name":"Ruth and Bruch Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naama","family":"Srebnik","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Department of Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joul","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of 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