eP160: Bilateral oophorectomy and the risk of breast cancer in women with a pathogenic variant in BRCA1: A reappraisal

There is a lack of consensus on whether preventive bilateral oophorectomy impacts the risk of developing breast cancer among women with a pathogenic BRCA1 variant (variant hereafter). The differing results might be attributed to various biases, specifically, cancer-induced testing bias due to the inclusion of prevalent cases. Thus, we conducted two complementary matched case-control analyses of our international cohort to evaluate the association of bilateral oophorectomy and BRCA1-breast cancer using two analytic approaches. Women with a BRCA1 variant who had sought genetic testing because of a personal or family history of breast and/or ovarian cancer. A research questionnaire was administered every two years to collect detailed information on various exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (ie, those diagnosed prior to study entry) (n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (ie, those diagnosed with breast cancer in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer with bilateral oophorectomy (with or without salpingectomy). In the first approach (including prevalent cases), there was a significant inverse association between oophorectomy and the risk of developing breast cancer (adjusted OR = 0.43; 95%CI 0.34-0.55; P < 00001). The level of risk reduction was significant both for women diagnosed with breast cancer prior to age 50 (OR = 0.38; 95%CI 0.28-0.52; P < 0.0001) and after age 50 (OR = 0.56; 95%CI 0.36-0.83; P = 0.004). In the second approach (including incident cases), there was no association between oophorectomy and risk of breast cancer (adjusted OR = 1.21; 95%CI 0.87-1.70; P = 0.26). The association did not vary significantly by age at oophorectomy, country of residence or timing of oophorectomy (prior to or following study enrollment). There was no significant association in the analysis stratified by age at diagnosis or time since oophorectomy. The two analyses demonstrate how the inclusion of women with a personal history of breast cancer prior to ascertainment (ie, cancer-induced testing bias) likely impacts upon the association of oophorectomy and BRCA1-breast cancer risk. Based on the collective evidence, we conclude that oophorectomy is unlikely to be a determinant of breast cancer risk in BRCA1 variant carriers. We endorse the recommendation that preventive bilateral salpingo-oophorectomy should be offered to women with a BRCA1 variant at age 35 to reduce the risk of ovarian and fallopian tube cancer.