Survival associated with recommended risk-reducing interventions for individuals with pathogenic variants in BRCA1/2.

Individuals with pathogenic variants in BRCA1 and BRCA2 face increased risks of breast and ovarian cancer and are recommended to follow lifelong cancer prevention strategies to reduce their cancer-related morbidity and mortality. Many of these strategies, including annual imaging, risk-reducing surgery, and select medication, have been shown to reduce cancer incidence or shift diagnosis toward early-stage disease. However, survival benefits of these commonly recommended interventions have been more difficult to demonstrate, and the quality of evidence supporting survival varies substantially across interventions. In this narrative review, we use the 2026 National Comprehensive Cancer Network (NCCN) guidelines as a framework to identify current breast and ovarian cancer risk-management strategies and evaluate the strength and certainty of the evidence supporting the potential survival benefit of each recommendation. We address methodological challenges that complicate interpretation of survival-associated outcomes, including limitations of observational study design and biases that restrict causal inference. We demonstrate that risk-reducing salpingo-oophorectomy has the most consistent evidence supporting improved overall survival, whereas evidence for breast cancer interventions may be limited by competing preventive strategies and concerns for self-selection and immortal time bias. Recognizing these differences may facilitate informed shared decision-making between patients and providers and identify priorities for future prospective research in hereditary breast and ovarian cancer.