Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers

Timothy R. Rebbeck, Albert M. Levin, Andrea Eisen, Carrie Snyder, Patrice Watson, Lisa Cannon-Albright, Claudine Isaacs, Olofunmilayo Olopade, Judy E. Garber, Andrew K. Godwin, Mary B. Daly, Steven A. Narod, Susan L. Neuhausen, Henry T. Lynch, Barbara L. Weber

Research output: Contribution to journalArticle

566 Scopus citations

Abstract

Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33- 0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12- 0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

Original languageEnglish (US)
Pages (from-to)1475-1479
Number of pages5
JournalJournal of the National Cancer Institute
Volume91
Issue number17
DOIs
StatePublished - Sep 1 1999

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Rebbeck, T. R., Levin, A. M., Eisen, A., Snyder, C., Watson, P., Cannon-Albright, L., Isaacs, C., Olopade, O., Garber, J. E., Godwin, A. K., Daly, M. B., Narod, S. A., Neuhausen, S. L., Lynch, H. T., & Weber, B. L. (1999). Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. Journal of the National Cancer Institute, 91(17), 1475-1479. https://doi.org/10.1093/jnci/91.17.1475