Risk-Reducing Mastectomy Linked to Lower Mortality in BRCA1/2 Variant Carriers

A systematic review and network meta-analysis of five observational studies involving 7,937 women with pathogenic BRCA1 or BRCA2 variants compared risk-reducing mastectomy with breast screening. Mastectomy was associated with lower all-cause mortality, but the evidence was rated very low certainty and most studies had critical risk of bias.

Five observational studies included 7,937 BRCA1/2 variant carriers.
RRM was associated with lower all-cause mortality than screening.
Breast cancer mortality benefit versus MRI screening was not significant overall.
Evidence certainty was very low, with critical bias in four studies.

This systematic review and network meta-analysis assessed whether risk-reducing mastectomy (RRM) was associated with survival benefits independent of risk-reducing salpingo-oophorectomy (RRSO). It included five prospective or retrospective observational studies involving 7,937 women with pathogenic or likely pathogenic BRCA1 or BRCA2 variants and no previous breast or ovarian cancer. Analyses compared RRM with MRI-based screening, with or without mammography, and mammography alone, using RRSO-excluded or RRSO-adjusted estimates.

RRM was associated with lower all-cause mortality than MRI-based screening (hazard ratio [HR], 0.37; 95% CI, 0.22-0.63) and mammography alone (HR, 0.16; 95% CI, 0.08-0.32). Breast cancer–specific mortality was lower with RRM than with mammography alone (HR, 0.07; 95% CI, 0.01-0.44), but not significantly lower than with MRI-based screening (HR, 0.26; 95% CI, 0.05-1.35). In BRCA1-only analyses, RRM was associated with lower breast cancer–specific mortality than either screening approach.

The findings may inform individualized discussions of preventive surgery and screening, but do not establish a causal benefit. Risk of bias was critical in four studies, and certainty was very low across all five; the authors emphasize shared decision-making.

In practice

For women with pathogenic BRCA1 or BRCA2 variants and no prior breast or ovarian cancer, this analysis found RRM associated with lower all-cause mortality than MRI-based screening or mammography alone. Overall breast cancer–specific mortality was not significantly lower than with MRI-based screening. These results may support individualized discussions of preventive surgery alongside screening, but they do not establish that surgery causes improved survival: the evidence came from only five observational studies, certainty was very low, and four studies had critical risk of bias.

AI-generated clinical interpretation · Not editor-reviewed

AI summary · Not yet editor-reviewed

Is this summary clinically accurate?

Help fellow clinicians: your rating sends inaccurate summaries straight to our editors.

Source

JAMA Network Open: Survival After Risk-Reducing Mastectomy in Patients With Pathogenic Variants in BRCA1 and BRCA2 ↗

This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.