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

Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1089-96. doi: 10.1158/1055-9965.EPI-12-0201. Epub 2012 May 7.


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 (P(trend) < 0.0001) but not among BRCA2 (P(trend) ≥ 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; P(trend) < 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.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / etiology*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Menopause*
  • Middle Aged
  • Mutation / genetics*
  • Ovariectomy / adverse effects*
  • Prognosis
  • Risk Factors
  • Young Adult


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