Survival After Risk-Reducing Mastectomy in Patients With Pathogenic Variants in BRCA1 and BRCA2: A Network Meta-Analysis

BRCA1/2

Risk reduction by risk-reducing mastectomy compared with breast screening in BRCA1/BRCA2 pathogenic variant carriers

This network meta-analysis assesses the association of risk-reducing mastectomy (RRM), MRI-based screening and mammography alone with mortality in carriers of BRCA1 or BRCA2 pathogenic variants, using estimates adjusted for risk-reducing salpingo-oophorectomy (RRSO). Five observational studies totalling 7,937 women without prior breast or ovarian cancer were included. RRM was associated with lower all-cause mortality than MRI-based screening (HR 0.37; 95% CI 0.22-0.63) and mammography alone (HR 0.16; 95% CI 0.08-0.32). For breast cancer-specific mortality, the difference was significant only against mammography alone (HR 0.07), except in BRCA1 carriers, in whom RRM also outperformed MRI-based screening (HR 0.13; 95% CI 0.03-0.66). Risk of bias was critical for 4 studies and certainty of evidence was rated very low for all 5.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value lies in separating the effect of mastectomy from that of salpingo-oophorectomy, a major confounder for this question, and the clearest signal concerns BRCA1 carriers. However, very low certainty, critical risk of bias in four of five studies and very low HRs from observational data mean these figures cannot be presented as a proven survival gain. They inform shared decision-making without settling the comparison with well-conducted MRI screening.

Analysis by Dr Thibaut Benquey