Do Risk-Reducing Operations Lower the Risk of Death in BRCA Mutation Carriers?

BRCA1 and BRCA2 mutation carriers have long faced uncertainty over the survival effects of risk-reducing surgery (prophylactic mastectomy and salpingo-oophorectomy). A large international study presented at SABCS 2024 and ultimately published in May 2025 in The Lancet Oncology provides an answer through striking, robust scientific data.

BRCA Mutations and Cancer Risk

BRCA1 and BRCA2 are tumor suppressor genes responsible for DNA repair. In these genes, inherited mutations substantially increase the risk of various tumors in women, particularly breast and ovarian cancers. BRCA mutations account for 5-10% of all breast cancer cases.

What Are Risk-Reducing (Prophylactic) Operations?

• Risk-Reducing Mastectomy (RRM): Surgical removal of the breasts to prevent breast cancer from developing.

• Risk-Reducing Salpingo-Oophorectomy (RRSO): Surgical removal of the ovaries and fallopian tubes.

The BRCA BCY Collaboration Study and Its Main Findings

The BRCA Breast Cancer in the Young (BCY) Collaboration is a retrospective cohort study conducted worldwide at 109 centers. It assessed the outcomes in this international cohort.

Between 2000-2020, women carrying BRCA1 or BRCA2 mutations who were diagnosed with stage I-III invasive breast cancer before age 40 were identified. A total of 5290 women were included in this analysis.

1. Risk-Reducing Mastectomy (RRM)

• Number of patients undergoing the procedure: 2910 (55%)

• Risk of death: 35% reduction (aHR: 0.65; 95% CI: 0.53–0.78)

• 20-year mean survival: 17.89 years (RRM) versus 16.65 years (without RRM)

2. Risk-Reducing Salpingo-Oophorectomy (RRSO)

• Number of patients undergoing the procedure: 2782 (52.6%)

• Risk of death: 42% reduction (aHR: 0.58; 95% CI: 0.48–0.71)

• 20-year mean survival: 17.73 years (RRSO) versus 16.67 years (without RRSO)

These findings indicate that both surgical procedures provide substantial, independent survival benefits.

Subgroup Findings

• BRCA1 Carriers and Triple-Negative Breast Cancer: RRSO provided a more pronounced benefit in this group.

• BRCA2 Carriers and Patients with Luminal Subtypes: A benefit was observed, but it was more limited.

Clinical and Psychosocial Implications

Opportunities for More Comprehensive Counseling

The data from this study substantially support communication between physicians and patients when making decisions about risk-reducing surgery.

Psychological Effects

Decisions about RRM and RRSO can have significant psychosocial effects, especially for young women. Perceptions of bodily integrity, sexuality, fertility, and the need for social support should be carefully addressed throughout this process.

Conclusion and Commentary

In women carrying BRCA1/2 mutations who were diagnosed with breast cancer at a young age, risk-reducing operations significantly improve overall survival, with statistically strong results. The study can also be considered a milestone as the largest data-based analysis conducted worldwide on this subject.

These findings should be considered in a patient-centered, individualized approach to risk management. Genetic counseling, surgical planning, oncological follow-up, and psychosocial support should be organized through a multidisciplinary approach.