Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy

J Natl Cancer Inst. 2018 Feb 1;110(2). doi: 10.1093/jnci/djx159.

Abstract

It has recently been shown that the risk of a rare subtype of endometrial carcinoma (serous type) in women carrying a germline BRCA1/2 pathogenic variant is increased. We assessed the incidence of serous endometrial carcinoma in an independent prospective cohort study of 369 BRCA1/2 women (1779 woman-years of follow-up) who underwent risk-reducing salpingo-oophorectomy by laparoscopy. This occurrence in two BRCA1 carriers led us to estimate that BRCA1/2 carriers present a higher risk than the control population (standardized incidence ratio = 32.2, 95% confidence interval = 11.5 to 116.4, P < .001, two-sided chi-square test, 1 degree of freedom). In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis. Prophylactic hysterectomy could be discussed with informed women through a shared decision-making process although the estimated 3% life-long risk is moderate. Additional studies are required to establish future prophylactic surgery guidelines.

MeSH terms

  • BRCA1 Protein
  • BRCA2 Protein
  • Cohort Studies
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / prevention & control
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / prevention & control
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Ovariectomy / methods*
  • Prospective Studies
  • Salpingectomy / methods*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human