Risk of uterine cancer for BRCA1 and BRCA2 mutation carriers

Eur J Cancer. 2017 Oct:84:114-120. doi: 10.1016/j.ejca.2017.07.004. Epub 2017 Aug 10.

Abstract

Background: Whether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery.

Aim: This multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population.

Methods: Eligible 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.

Results: Of 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.

Conclusions: Our findings are consistent with those from most other reports and do not support routine risk-reducing hysterectomy for BRCA1 and BRCA2 mutation carriers.

Keywords: BRCA1; BRCA2; Endometrial cancer; Oophorectomy; Risk-reducing surgery; Uterine cancer.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia / epidemiology
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote*
  • Humans
  • Hysterectomy
  • Incidence
  • Middle Aged
  • Mutation*
  • New Zealand / epidemiology
  • Phenotype
  • Prospective Studies
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Risk Reduction Behavior
  • Time Factors
  • Uterine Neoplasms / diagnosis
  • Uterine Neoplasms / epidemiology
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / prevention & control

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor