Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers

Simple Summary Prophylactic interventions are critical for BRCA1/2 mutation carriers to reduce the risks of hereditary breast and ovarian cancer (HBOC). This systematic review and meta-analysis synthesizes data on the efficacy of various preventative strategies. The analysis incorporated 21 studies involving risk-reducing surgeries (RRS), chemoprevention, and screening. Findings indicate a substantial reduction in breast and ovarian cancer incidence and mortality among BRCA1/2 carriers following RRS, particularly mastectomy and oophorectomy, compared to chemoprevention. This study underscores the necessity of tailored interventions, especially considering the varied protective effects between BRCA1 and BRCA2 mutation carriers. This review aids in informing clinical decisions and underscores the importance of context-specific uptake rates in cost-effective evaluations.Abstract Background: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. Methods: A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle-Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. Results: A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. Conclusions: Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.