title: Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
abstract: 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.
  
  
  CONCLUSIONS
  Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.
authors.affiliation: Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kim-Sing
authors.forename: Susan
authors.initials: S
authors.lastname: Neuhausen
authors.forename: Rochelle
authors.initials: R
authors.lastname: Demsky
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Peter
authors.initials: P
authors.lastname: Ainsworth
authors.forename: Leigha
authors.initials: L
authors.lastname: Senter
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weitzel
authors.forename: Dawna M
authors.initials: DM
authors.lastname: Gilchrist
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Dana
authors.initials: D
authors.lastname: Zakalik
authors.forename: Christian
authors.initials: C
authors.lastname: Singer
authors.forename: Taya
authors.initials: T
authors.lastname: Fallen
authors.forename: Ophira
authors.initials: O
authors.lastname: Ginsburg
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010052:Ovariectomy / Q000009:adverse effects*; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human