BRCA1 或 BRCA2 基因中携带种系致病性变异（“突变”）的女性患子宫内膜癌的风险是否升高尚未确定。我们对 4959 名既往无子宫内膜癌病史的 BRCA 突变携带者进行了前瞻性分析。癌症（乳腺癌或黑色素瘤除外）和完整的子宫。经过平均 6.7 年的随访，诊断出 38 例子宫内膜癌病例； BRCA1 携带者中有 30 名，BRCA2 携带者有 8 名。诊断时的平均年龄为 58.4 岁（范围 46.8-76.1 岁）。大多数为子宫内膜样亚型 (n = 16)，其次是混合子宫内膜样和浆液性亚型 (n = 4)、浆液性亚型 (n = 3) 或透明细胞亚型 (n = 1)（缺失 = 13）。从40岁到70岁，BRCA1突变携带者的累积发病率为3.4%，BRCA2突变携带者的累积发病率为1.6%。既往使用他莫昔芬与风险显着增加两倍相关（HR = 2.24；95% CI 1.10-4.55）。外源激素使用、卵巢切除术、吸烟或40岁时BMI与风险之间没有显着相关性（P≥0.32）。与一般人群相比，我们观察到年轻BRCA1突变携带者的子宫内膜癌发病率较高；然而，终生风险相似。既往接触过他莫昔芬的女性的风险显着增加。这些发现是有依据的。少数事件案例，并需要对我们的老龄化群体进行额外随访进行确认。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Whether or not women who harbor a germline pathogenic variant ('mutation') in the BRCA1 or BRCA2 genes are at elevated risk of developing endometrial cancer is yet to be determined.We conducted a prospective analysis of 4959 BRCA mutation carriers with no prior history of cancer (except for breast or melanoma) and an intact uterus.After a mean of 6.7 years of follow-up there were 38 incident cases of endometrial cancer diagnosed; 30 among BRCA1 carriers and eight among BRCA2 carriers. The mean age at diagnosis was 58.4 years (range 46.8-76.1). The majority were of the endometrioid subtype (n = 16), followed by mixed endometroid and serous (n = 4), serous (n = 3) or clear cell (n = 1) (missing = 13). The cumulative incidence from age 40 to age 70 was 3.4% for BRCA1 carriers and was 1.6% for BRCA2 mutation 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 between exogenous hormone use, oophorectomy, smoking or BMI at age 40 and risk (P ≥ 0.32).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.Copyright © 2024 Elsevier Inc. All rights reserved.