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

AbstractBACKGROUND:
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.
AuthorsJoanne 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 Fallen, Ophira Ginsburg, Tomasz Huzarski, Ping Sun, Steven A Narod
JournalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 21 Issue 7 Pg. 1089-96 (Jul 2012) ISSN: 1538-7755 [Electronic] United States
PMID22564871 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright©2012 AACR
Chemical References
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
Topics
  • 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

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