Abstract P6-09-01: Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk using a prospective family study cohort (ProF-SC)
Authors: Terry MB , Phillips KA , Daly MB , Andrulis IL , Liao Y , Ma X , Zeinomar N , MacInnis RJ , Dite GS , John EM , Buys SS , Hopper JL 
Published: February 2018

Abstract
Background: Whether risk-reducing salpingo oophorectomy (RRSO) reduces breast cancer risk in addition to reducing ovarian cancer risk is controversial with some arguing that the previous evidence of a reduction in breast cancer risk from RRSO was due to bias. Evidence from independent prospective cohorts of high-risk women is needed to resolve this controversy.
Methods: Using a prospective family study cohort of 17,810 women unaffected with breast cancer at baseline, we examined the association between RRSO and breast cancer risk using Cox Proportional Hazards models. We compared results estimating RRSO as a non-time-dependent variable to results treating RRSO as a time-dependent variable, because failing to account for the time-varying nature of a covariate person- time prior to RRSO, should it exist, will incorrectly attribute the cancer-free person-time to RRSO. We separately examined the association with RRSO in BRCA1 and BRCA2 mutation carriers and non-carriers, and further performed gene-stratified analyses in women with BRCA1 and BRCA2 only. We also assessed multiplicative interactions with underlying familial risk profile (FRP), defined as total lifetime risk estimated from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model.
Results: During a median 10.7 years of follow-up (maximum 23.7 years), we observed 1,040 incident cases of breast cancer with an average age at diagnosis of 55.8 years and average age at enrollment into the cohort of 46.8 years. A total of 2434 (14%) women reported at baseline having a RRSO. We observed decreased risk of breast cancer associated with RRSO for both BRCA1(N= 650) and BRCA2(N=557) mutation carriers when RRSO was treated as a fixed covariate (HR= 0.60, 95% CI=0.40-0.92 and HR= 0.40, 95%CI = 0.23-0.69, respectively). In contrast, when we treated RRSO as a time-varying covariate, for both BRCA1 and BRCA2 carriers, we no longer observed a decreased risk for BRCA1 and BRCA2 carriers (HR= 1.67, 95% CI=1.05-2.67 and HR= 0.97, 95%CI = 0.53-1.80, respectively). There was no association between RRSO and breast cancer risk for non-carriers (N=16,603), whether we treated RRSO as a fixed or time varying covariate (HR= 0.88, 95% CI=0.72-1.08 and HR= 1.06, 95%CI = 0.85-1.30, respectively).
Conclusions: Our findings provide an independent replication that the reduced risk of breast cancer previously observed in BRCA1 and BRCA2 mutation carrier women may be from bias in counting person-time. Clinical management of high-risk women should counsel based on the reduced risk of ovarian cancer from RRSO, but not breast cancer.
Citation Format: Terry MB, Phillips KA, Daly MB, Andrulis IL, Liao Y, Ma X, Zeinomar N, MacInnis RJ, Dite GS, John EM, Buys SS, Hopper JL. Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk using a prospective family study cohort (ProF-SC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-01.