Original ResearchRisk of uterine cancer for BRCA1 and BRCA2 mutation carriers

- Five cases of uterine cancers were reported in 828 BRCA1 and BRCA2 mutation carriers.
- Three of the five affected women had previous tamoxifen treatment for breast cancer.
- The standardised incidence ratio for uterine cancer in mutation carriers was 2.45 (95% confidence interval: 0.80-5.72; P = 0.11).
- There were no cases of the serous subtype of uterine cancer in this study.
- These data do not justify risk-reducing hysterectomy in BRCA1 and BRCA2 mutation carriers.

BackgroundWhether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery.AimThis multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population.MethodsEligible mutation carriers were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) cohort study, had a uterus present and no history of uterine cancer at cohort entry. Epidemiological, lifestyle and clinical data were collected at cohort entry and updated three-yearly. Cancer events were verified using pathology reports. Follow-up was censored at death or last contact. Relative risk of uterine cancer was estimated using the standardised incidence ratio (SIR), with the expected number of cases determined using population-based data for Australia.ResultsOf 1,111 mutation carriers in kConFab, 283 were excluded due to prior hysterectomy (N = 278), prior uterine cancer (N = 2) or being non-residents (N = 3). After a median follow-up of 9.0 years, five incident uterine cancers were reported in the 828 eligible women (419 had prior breast cancer and 160 had prior tamoxifen use), compared to 2.04 expected (SIR = 2.45; 95% confidence interval [CI]: 0.80-5.72; P = 0.11). In 438 BRCA1 mutation carriers and 390 BRCA2 mutation carriers, three and two incident cases of uterine cancer were reported, respectively, compared to 1.04 expected (SIR = 2.87; 95% CI: 0.59-8.43; P = 0.18) and 0.99 expected (SIR = 2.01; 95% CI: 0.24-7.30; P = 0.52), respectively. All cases were endometrioid subtype, International Federation of Gynaecology and Obstetrics stage I-II disease. No serous uterine cancers were reported.ConclusionsOur findings are consistent with those from most other reports and do not support routine risk-reducing hysterectomy for BRCA1 and BRCA2 mutation carriers.