Risk-Reducing Bilateral Mastectomy and Mortality in Carriers of BRCA1 and BRCA2 Variants: A Systematic Review and Meta-Analysis
A partir d'une revue systématique de la littérature publiée jusqu'en mai 2025 (6 études, 6 135 femmes), cette méta-analyse évalue l'effet, sur la mortalité, d'une mastectomie bilatérale prophylactique chez les femmes porteuses d'une mutation BRCA
Risk-reducing bilateral mastectomy reduces the incidence of breast cancer in female carriers of the BRCA pathogenic variants, but its association with mortality remains uncertain.To evaluate the association between risk-reducing bilateral mastectomy and overall and breast cancer–specific mortality in female carriers of BRCA pathogenic variants.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.Eligible studies compared female carriers of BRCA1 and BRCA2 pathogenic variants who underwent risk-reducing bilateral mastectomy with those who did not and reported overall mortality or breast cancer–specific mortality. Studies including patients with a history of breast cancer were excluded.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—of Interventions, version 2). Odds ratios (ORs) and hazard ratios (HRs) were pooled using fixed- and random-effects models according to methodological assessment.Overall and breast cancer–specific mortality.Six observational studies met the inclusion criteria, comprising 6135 carriers of the BRCA1 or BRCA2 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; P < .001) and adjusted (HR, 0.37; 95% CI, 0.23-0.60; P < .001) analyses. Breast cancer–specific mortality was also reduced (OR, 0.19; 95% CI, 0.08-0.47; P < .001; HR, 0.14; 95% CI, 0.04-0.49; P = .002).Risk-reducing bilateral mastectomy was associated with lower overall and breast cancer–specific mortality in carriers of the BRCA 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.
JAMA Surgery , résumé, 2026