TOPLINE:

Risk-reducing bilateral mastectomy is associated with a 63% reduction in overall mortality and an 81%-86% reduction in breast cancer-specific mortality among women who carry BRCA pathogenic variants.

METHODOLOGY:

• Women with pathogenic variants in BRCA1 or BRCA2 have a roughly 70% lifetime risk of developing breast cancer. Risk-reducing bilateral mastectomy greatly decreases that risk, but its effects on mortality are unclear. Because of that, guidance on counseling patients emphasizes that the primary aim of risk-reducing bilateral mastectomy is to prevent the development of breast cancer.
• To investigate the potential mortality benefit, researchers conducted a systematic review and meta-analysis of six observational studies. They included a total of 6135 female carriers of BRCA1 or BRCA2 variants (median age, 38 years), of whom 2558 underwent risk-reducing bilateral mastectomy, while 3577 did not.
• Primary outcomes were overall mortality and breast cancer-specific mortality. Odds ratios (ORs) and hazard ratios (HRs) were pooled using fixed- and random-effects models. Median follow-up was 75.6 months, with a duration of up to 127 months.

TAKEAWAY:

• Carriers who underwent risk-reducing bilateral mastectomy were less likely to die from breast cancer or any cause vs carriers who did not have the procedure. Their overall mortality was reduced in both unadjusted (OR, 0.38; P < .001) and adjusted (HR, 0.37; P < .001) analyses. A larger reduction was seen in breast cancer-specific mortality (OR, 0.19; P < .001, and HR, 0.14; P = .002).
• Among BRCA1 carriers specifically, risk-reducing bilateral mastectomy was associated with a significant reduction in breast cancer-specific mortality (HR, 0.15; P = .003). Data were insufficient to look at BRCA2 carriers in isolation.
• A trial sequential analysis was conducted post hoc for the OR results and confirmed significant associations. Overall, the authors rated the certainty of the evidence as low due to the observational nature of the studies.

IN PRACTICE:

These results, the authors of the study wrote, “challenge the current knowledge” by demonstrating a mortality benefit for BRCA carriers who undergo this procedure.“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,” they concluded.

SOURCE:

The study, led by Cathal O’Reilly, MBBS, MCh, St Vincent’s University Hospital, Dublin, Ireland, was published in JAMA Surgery.

LIMITATIONS:

The meta-analysis included a small number of studies and relied heavily on larger studies, with few mortality events in some of the smaller studies. Heterogeneity in reporting and adjustment for confounders, together with a serious risk for bias in several studies, were considerable limitations, the authors of the study noted.

DISCLOSURES:

The authors of the study reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.