Risk-Reducing Mastectomy in BRCA1/2 and Other High-Risk Gene Carriers: Current Evidence and Practical Guidance

Area of Science:

• Oncology
• Genetics
• Preventive Medicine

Background:

• Women with pathogenic variants in high/moderate-penetrance genes (e.g., BRCA1/2, TP53) have substantially increased breast cancer risk.
• Risk-reducing mastectomy (RRM) is a surgical option shown to decrease breast cancer incidence by ~90% in observational studies.

Purpose of the Study:

• To review current evidence and guidelines on risk-reducing mastectomy (RRM) for hereditary breast cancer.
• To clarify the benefits, limitations, and controversies surrounding RRM.
• To aid informed, patient-centered decision-making for high-risk individuals.

Main Methods:

• Literature review integrating current evidence and evolving guidelines.
• Analysis of observational cohort studies and meta-analyses on RRM efficacy.
• Discussion of factors influencing RRM decision-making.

Main Results:

• RRM substantially reduces breast cancer incidence in high-risk women.
• The survival advantage of RRM is not definitively established due to study limitations.
• Guidance for moderate-penetrance genes relies on risk modeling and expert consensus.

Conclusions:

• RRM is a viable option for high-risk women, but requires individualized, multidisciplinary decision-making.
• Patient age, family plans, culture, and healthcare systems influence RRM choices.
• Further research is needed to clarify RRM's survival benefits and address knowledge gaps.