Network meta-analysis of survival after risk-reducing mastectomy in patients with pathogenic BRCA1/2 variants

The independent survival benefit of risk-reducing mastectomy (RRM), separate from risk-reducing salpingo-oophorectomy (RRSO), among patients with pathogenic variants (PVs) in BRCA1 and BRCA2 genes is not clear. A network meta-analysis of 5 observational studies with 7937 patients who underwent RRM or breast cancer screening (MRI-based with or without mammography, or mammography alone), with RRSO excluded by design or adjusted for in multivariable analysis. RRM was associated with lower all-cause mortality compared with MRI-based screening (HR 0.37; 95% CI 0.22-0.63) and mammography alone (0.16; 0.08-0.32). RRM was also associated with lower breast cancer-specific mortality compared with mammography alone (HR 0.07; 95% CI 0.01-0.44) but not compared with MRI-based screening (0.26; 0.05-1.35). In BRCA1-only analyses, RRM was associated with lower breast cancer-specfic mortality compared with MRI-based screening (HR 0.13; 95% CI 0.03-0.66) and mammography alone (0.03; 0.00-0.15). Risk of bias was critical for 4 studies, and certainty of evidence was rated as very low for all 5 studies. The authors conclude that RRM was associated with lower all-cause mortality compared with breast cancer screening among females with PVs in BRCA1 or BRCA2 (graphical abstract).