Risk-Reducing Oophorectomy and Breast Cancer Risk Across the Spectrum of Familial Risk

Abstract

There remains debate about whether risk-reducing salpingo-oophorectomy (RRSO), which reduces ovarian cancer risk, also reduces breast cancer risk. We examined the association between RRSO and breast cancer risk using a prospective cohort of 17 917 women unaffected with breast cancer at baseline (7.2% known carriers of BRCA1 or BRCA2 mutations). During a median follow-up of 10.7 years, 1046 women were diagnosed with incident breast cancer. Modeling RRSO as a time-varying exposure, there was no association with breast cancer risk overall (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.87 to 1.24) or by tertiles of predicted absolute risk based on family history (HR = 0.68, 95% CI = 0.32 to 1.47, HR = 0.94, 95% CI = 0.70 to 1.26, and HR = 1.10, 95% CI = 0.88 to 1.39, for lowest, middle, and highest tertile of risk, respectively) or for BRCA1 and BRCA2 mutation carriers when examined separately. There was also no association after accounting for hormone therapy use after RRSO. These findings suggest that RRSO should not be considered efficacious for reducing breast cancer risk.

Figure 1.

Model comparison for women who were unaffected at baseline, ProF-SC. Adjusted for age at baseline, race/ethnicity, study center, and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) score. Time-dependent models count individuals as unexposed before risk-reducing salpingo-oophorectomy (RRSO) and exposed after RRSO; non-time-dependent models treat RRSO as a fixed effect. A) summarizes the results from models treating RRSO as both a fixed and time varying exposure for the overall cohort stratified by tertile of predicted absolute risk of breast cancer as estimated by BOADICEA. B) summarizes results from models treating RRSO as both a fixed and time varying exposure for BRCA1 mutation carriers, BRCA2 mutation carriers, and non-carriers. C) presents time-dependent models for non-carriers stratified by age at RRSO or by age at hormone replacement therapy (HRT) use after RRSO. D) presents time-dependent models for women in the upper tertile of absolute risk of breast cancer as estimated by BOADICEA, stratified by age at RRSO or by age at hormone replacement therapy (HRT) use after RRSO. All panels present models starting follow-up time at at age 25 years or at baseline age.