In women with pathogenic variants in BRCA1 and BRCA2, risk-reducing salpingo-oophorectomy (RRSO) to help avoid ovarian cancer also appears to reduce breast-cancer risk, particularly within five years of surgery, according to a new analysis. Women with these variants are at high risk of developing breast cancer and ovarian cancer, Dr. Laurent Briollais of Sinai Health System, in Toronto, and colleagues note in JAMA Oncology. Although risk-reducing mastectomy may be offered, the effect of RRSO on breast cancer risk is not well defined, they add. Early studies consistently showed risk reduction, but these were later refuted by analyses that considered RRSO as a time-varying covariate. To investigate further, the researchers studied registry data on 876 families; 498 families (2,650 individuals) carried an inherited pathogenic variant in BRCA1 and 88% of probands were white. The remaining 378 families (1,925 individuals) had an inherited pathogenic variant in BRCA2 and 79% of probands were white. The proportion of family members who undertook RRSO was 6.3% in BRCA1 families and 7.5% in BRCA2 families. Within five years of surgery, RRSO was associated with a significantly reduced risk of breast cancer for both BRCA1-mutation carriers (hazard ratio, 0.28) and for BRCA2-mutation carriers (HR, 0.19). At more than five years after surgery, the corresponding hazard ratios were 0.64 and 0.76, with only the former representing a significant reduction in mortality. Carriers of BRCA1 and BRCA2 pathogenic variants who underwent RRSO at the age of 40 had a cause-specific cumulative risk of breast cancer of 49.7% and 52.7%, respectively, by age 70 years. For women without RRSO, the proportions were 61.0% and 54.0%. The researchers caution they did not adjust for hormone therapy after RRSO in their analyses. But they point out that such therapy is associated with increased breast-cancer risk in the general population, so that it would be more likely to attenuate the risk reduction associated with RRSO than to exaggerate it. "Further work is needed to confirm this result in larger cohorts and to assess carefully the optimal timing of RRSO uptake," they conclude. Gynecologic oncologist Dr. C. Bethan Powell of Kaiser Permanente San Francisco, who was not involved in the study, told Reuters Health by email, "This is a well-done study with a relevant question for women with BRCA mutations. How much does having salpingo-oophorectomy . . . benefit women for their breast cancer risk?" "Many women," she pointed out, "are reluctant to have ovaries removed because of the impact of menopause. The authors show that there is a reduction in breast cancer risk for both BRCA1 and BRCA2 carriers, particularly in the first five years after oophorectomy. There is a lifelong reduction in breast cancer for women who carry a BRCA1 mutation. This contributes to decision making for women regarding the benefit of having ovaries removed in the premenopausal age range." Dr. Briollais did not respond to requests for comments. —David Douglas Source
