Incidence of endometrial cancer in BRCA mutation carriers

Objective. Whether or not women who harbor a germline pathogenic variant ('mutation') in theBRCA1orBRCA2genes are at elevated risk of developing endometrial cancer is yet to be determined. Methods. We conducted a prospective analysis of 4959BRCAmutation carriers with no prior history of cancer(except for breast or melanoma) and an intact uterus. Results. After a mean of 6.7 years of follow-up there were 38 incident cases of endometrial cancer diagnosed;30 amongBRCA1carriers and eight amongBRCA2carriers. The mean age at diagnosis was 58.4 years (range46.8-76.1). The majority were of the endometrioid subtype (n= 16), followed by mixed endometroid and se-rous (n= 4), serous (n= 3) or clear cell (n= 1) (missing = 13). The cumulative incidence from age 40 toage 70 was 3.4% forBRCA1carriers and was 1.6% forBRCA2mutation carriers. Prior tamoxifen use was associated with a significant two-fold increased risk (HR = 2.24; 95% CI 1.10-4.55). There was no significant association be- tween exogenous hormone use, oophorectomy, smoking or BMI at age 40 and risk (P P >= 0.32). Conclusions. Compared to the general population, we observed higher rates of endometrial cancer among young BRCA1 mutation carriers; however, lifetime risks were similar. Women with prior tamoxifen exposure were at a significantly increased risk. These findings were based. on a small number of incident cases and require confirmation with additional follow-up of our aging cohort. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.