Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations

Timothy R. Rebbeck, Henry T. Lynch, Susan L. Neuhausen, Steven A. Narod, Laura Van't Veer, Judy E. Garber, Gareth Evans, Claudine Isaacs, Mary B. Daly, Ellen Matloff, Olufunmilayo I. Olopade, Barbara L. Weber

Research output: Contribution to journalArticlepeer-review

1357 Scopus citations

Abstract

Background: Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. Methods: A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. Results: Six women who underwent prophylactic oophorectomy (2.3 percent) received a diagnosis of stage I ovarian cancer at the time of the procedure; two women (0.8 percent) received a diagnosis of papillary serous peritoneal carcinoma 3.8 and 8.6 years after bilateral prophylactic oophorectomy. Among the controls, 58 women (19.9 percent) received a diagnosis of ovarian cancer, after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio, 0.04; 95 percent confidence interval, 0.01 to 0.16). Of 99 women who underwent bilateral prophylactic oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2 percent), as compared with 60 (42.3 percent) in the control group (hazard ratio, 0.47; 95 percent confidence interval, 0.29 to 0.77). Conclusions: Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCA2 mutations.

Original languageEnglish
Pages (from-to)1616-1622
Number of pages7
JournalNew England Journal of Medicine
Volume346
Issue number21
DOIs
StatePublished - May 23 2002

Keywords

  • Adult
  • Breast Neoplasms/epidemiology
  • Case-Control Studies
  • Cystadenocarcinoma, Serous/epidemiology
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Germ-Line Mutation
  • Humans
  • Incidence
  • Middle Aged
  • Ovarian Neoplasms/epidemiology
  • Ovariectomy
  • Peritoneal Neoplasms/epidemiology
  • Proportional Hazards Models
  • Risk

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