Prospective cohort study of survival outcomes with or without risk-reducing mastectomy in BRCA1 and BRCA2 pathogenic variant carriers

Many women carrying pathogenic variants of BRCA1 or BRCA2 genes (pvBRCA1/2) elect to undergo bilateral risk-reducing mastectomy (BRRM). A prospective cohort study at the University of Manchester (UK) compared long-term oncology outcomes in women with pvBRCA1/2 undergoing BRRM (n=460) versus imaging surveillance (n=745). Median age in the two groups was 37.2 and 38.5 years (p=0.06). Follow-up totalled 4.652 woman-years after BRRM. Overall annual incidence rate of breast cancer was 2.4%, falling to 0.15% after BRRM, a 94% reduction compared with surveillance alone (p<0.001). There were nine occult cancers diagnosed at BRRM (2%). Breast cancer-specific deaths were similar in the BRRM and surveillance groups (two and four deaths, respectively; p=0.36; 4,634 and 5,419 woman-years of follow-up, respectively). Proportionally, death from breast cancer were similar to death from ovarian cancer in both groups. The authors conclude that breast cancer-specific survival and overall survival are unlikely to be compromised in women electing surveillance over BRRM; however, breast cancer incidence rates are significantly reduced after BRRM compared with imaging surveillance.