Uterine cancer in Jewish Israeli BRCA1/BRCA2 mutation carriers.

Laitman Y1, Michaelson-Cohen R2, Levi E2, Chen-Shtoyerman R3, Reish O4, Josefsberg Ben-Yehoshua S3, Bernstein-Molho R5,6, Keinan-Boker L7,8, Rosengarten O9, Silverman BG7, Perri T10,6, Korach J10,6, Mor P2, Ephrat Ben-Baruch N11, Levy Lahad E2, Friedman E1,6; Israeli Consortium of Hereditary Breast Cancer.

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Abstract

BACKGROUND:

BRCA1/BRCA2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved.

METHOD:

Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/BRCA2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count.

RESULTS:

Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer).

CONCLUSION:

Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.