Ductal carcinoma in situ and BRCA mutations: Association and risk factors

Abstract

10016 Introduction: Ductal carcinoma in situ (DCIS) has been associated with BRCA mutations. Factors associated with the presence of mutations are not well defined. Methods: BRCA founder mutation status was determined in 3 groups of women with DCIS: 1) a prevalent convenience sample of Ashkenazi Jewish (AJ) women (Sukumvanich SSO 2005), 2) an incident cohort of AJ women ascertained before breast surgery and 3) a clinical ascertainment of probands (P) with DCIS (53 AJ and 38 non-AJ) presenting to a cancer risk assessment service. For women in groups 1 and 2, BRCA founder mutation status was also determined in age-matched controls with invasive breast cancer (BC). Results: Within the prevalent ascertainment, 3/62 (4.8%) women with DCIS and 15/130 (11.5%) controls with invasive BC had BRCA mutations. In the incident cohort, 0/58 (0%) women with DCIS and 6/116 (5.2%) controls with invasive BC had BRCA mutations (combined OR 3.6, 95% CI 1.1–12.5, p 0.04). In the clinical ascertainment of AJ women with DCIS, mutations were identified in 4/35 (11.4%) P ≤ 50 yrs at dx and in 2/18 (11.1%) P > 50 yrs. The proportion of AJ P with mutations based on family history (FH) of BC and ovarian cancer (OC) is shown in the table. In AJ P with DCIS, FH of OC is strongly associated with BRCA mutations (adjusted OR 10.0, 95% CI 1.1–89.3, p 0.04). Among non-AJ P, no mutations were identified without a FH of OC or BC ≤ 50 yrs at dx. Conclusions: DCIS is associated with BRCA mutations in AJ women, but the prevalence is lower than in women with invasive cancer. FH of OC is a strong risk factor. [Table: see text] No significant financial relationships to disclose.