PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers
Among 2,482 women with BRCA1 or BRCA2 mutations, removing the ovaries and fallopian tubes was associated with 60% lower all-cause mortality, and no breast cancers occurred in the women who had preventive mastectomy.
The PROSE consortium followed 2,482 women with a BRCA1 or BRCA2 mutation at 22 centres in Europe and North America from 1974 to 2008, comparing outcomes in those who did and did not undergo risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO).
No breast cancers were diagnosed in the 247 women who had RRM over 3 years of follow-up, compared with 98 in the 1,372 who did not. RRSO was associated with lower risk of ovarian cancer, of first breast cancer in BRCA1 carriers, and with reduced all-cause mortality (10% vs 3%), breast cancer-specific mortality and ovarian cancer-specific mortality.
It was the first study to link risk-reducing surgery to a survival advantage and cemented RRSO as the standard recommendation for carriers by age 35-40 (BRCA1) or 40-45 (BRCA2).
- Risk-reducing mastectomy: 0 breast cancers in 247 women vs 98 in 1,372 without surgery
- RRSO associated with lower all-cause mortality: 3% vs 10% (HR 0.40, 95% CI 0.26-0.61)
- RRSO associated with lower breast cancer-specific mortality (HR 0.44) and ovarian cancer-specific mortality (HR 0.21)
- RRSO reduced ovarian cancer risk in women with no prior breast cancer (HR 0.28 in BRCA1 carriers)
For women who carry a BRCA mutation, preventive removal of the ovaries and tubes saves lives, and preventive mastectomy almost eliminates breast cancer. These are the strongest prevention effects in oncology, which is why finding carriers before they develop cancer matters so much.
- Observational; women choosing surgery may differ from those who do not (healthy-adopter bias)
- Follow-up after RRM was short (about 3 years)
- Surgical menopause has cardiovascular, bone and quality-of-life costs not captured here
- Later analyses questioned whether RRSO reduces breast cancer risk once ascertainment bias is addressed