Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Joanne Kotsopoulos, Jan Lubinski, Henry T. Lynch, Charmaine Kim-Sing, Susan Neuhausen, Rochelle Demsky, William D. Foulkes, Parviz Ghadirian, Nadine Tung, Peter Ainsworth, Leigha Senter, Beth Karlan, Andrea Eisen, Charis Eng, Jeffrey Weitzel, Dawna M. Gilchrist, Joanne L. Blum, Dana Zakalik, Christian Singer, Taya FallenOphira Ginsburg, Tomasz Huzarski, Ping Sun, Steven A. Narod

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Background: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. Methods: We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. Results: The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ =-0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (Ptrend <0.0001) but not among BRCA2 (Ptrend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; Ptrend <0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006). Conclusions: These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. Impact: Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.

Original languageEnglish (US)
Pages (from-to)1089-1096
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number7
StatePublished - Jul 2012

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology


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