title: Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study.
abstract: BACKGROUND
  Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown.
  
  
  METHODS
  We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach.
  
  
  RESULTS
  Breast cancer risk was not significantly related to age at menopause [hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; >or=55 years, 1.12 [0.12-5.02], as compared with premenopausal women]. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity.
  
  
  CONCLUSIONS
  These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280 69120 Heidelberg, Germany. j.chang-claude@dkfz-heidelberg.de
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: Matti
authors.initials: M
authors.lastname: Rookus
authors.forename: Richard
authors.initials: R
authors.lastname: Brohet
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Davidson
authors.forename: Louise
authors.initials: L
authors.lastname: Izatt
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.forename: Laetitia
authors.initials: L
authors.lastname: Huiart
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Flora E
authors.initials: FE
authors.lastname: Van Leeuwen
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Jorunn
authors.initials: J
authors.lastname: Eyfjord
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008572:Menarche / Q000502:physiology*; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D012307:Risk Factors