{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:02:44Z","timestamp":1792389764086,"version":"4.4.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec id=\"ab-soi250089-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Risk-reducing bilateral mastectomy reduces the incidence of breast cancer in female carriers of the\n                      <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                      pathogenic variants, but its association with mortality remains uncertain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the association between risk-reducing bilateral mastectomy and overall and breast cancer\u2013specific mortality in female carriers of\n                      <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                      pathogenic variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>PubMed, Scopus, CINAHL, Embase, and CENTRAL were searched in May 2025, with English-language restriction and no date limit. Reference lists of included studies and relevant reviews were also examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>\n                      Eligible studies compared female carriers of\n                      <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n                      pathogenic variants who underwent risk-reducing bilateral mastectomy with those who did not and reported overall mortality or breast cancer\u2013specific mortality. Studies including patients with a history of breast cancer were excluded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>This meta-analysis followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Two authors independently performed study selection, data extraction, and risk of bias assessment (using Risk of Bias in Nonrandomized Studies\u2014of Interventions, version 2). Odds ratios (ORs) and hazard ratios (HRs) were pooled using fixed- and random-effects models according to methodological assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Overall and breast cancer\u2013specific mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six observational studies met the inclusion criteria, comprising 6135 carriers of the\n                      <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n                      variant. Weighted median age at inclusion was 38.0 years, with reported age ranges spanning 15.3 to 85.3 years. Risk-reducing bilateral mastectomy was associated with lower overall mortality in both unadjusted (OR, 0.38; 95% CI, 0.27-0.55;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) and adjusted (HR, 0.37; 95% CI, 0.23-0.60;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) analyses. Breast cancer\u2013specific mortality was also reduced (OR, 0.19; 95% CI, 0.08-0.47;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001; HR, 0.14; 95% CI, 0.04-0.49;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-soi250089-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>\n                      Risk-reducing bilateral mastectomy was associated with lower overall and breast cancer\u2013specific mortality in carriers of the\n                      <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                      variants. These findings support the role of risk-reducing bilateral mastectomy as a potentially life-extending intervention and may inform the shared decision-making discussions in these women.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamasurg.2025.5929","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:31:12Z","timestamp":1767803472000},"page":"260","source":"Crossref","is-referenced-by-count":8,"title":["Risk-Reducing Bilateral Mastectomy and Mortality in Carriers of\n                    <i>BRCA1<\/i>\n                    and\n                    <i>BRCA2<\/i>\n                    Variants"],"prefix":"10.1001","volume":"161","author":[{"given":"Cathal","family":"O\u2019Reilly","sequence":"first","affiliation":[{"name":"St Vincent\u2019s University Hospital, Breast Surgery, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer 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