title: Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
abstract: BACKGROUND
  Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2.
  
  
  METHODS
  We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided.
  
  
  RESULTS
  Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCA1 mutation carriers, ever use of oral contraceptives was associated with a modestly increased risk of breast cancer (OR = 1.20, 95% CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95% CI = 1.17 to 1.75).
  
  
  CONCLUSIONS
  Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
authors.affiliation: The Centre for Research on Women's Health, University of Toronto, 790 Bay Street, Toronto, Ontario M5G 1N8, Canada. steven.narod@swchsc.on.ca
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Jan
authors.initials: J
authors.lastname: Klijn
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
authors.forename: Pal
authors.initials: P
authors.lastname: Moller
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Barbara
authors.initials: B
authors.lastname: Weber
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.forename: Theresa
authors.initials: T
authors.lastname: Wagner
authors.forename: Mary
authors.initials: M
authors.lastname: Daly
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Peter
authors.initials: P
authors.lastname: Ainsworth
authors.forename: Hakan
authors.initials: H
authors.lastname: Olsson
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Michael
authors.initials: M
authors.lastname: Osborne
authors.forename: Fergus
authors.initials: F
authors.lastname: Couch
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Ellen
authors.initials: E
authors.lastname: Warner
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kim-Sing
authors.forename: Olufunmilayo
authors.initials: O
authors.lastname: Olopade
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Howard M
authors.initials: HM
authors.lastname: Saal
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weitzel
authors.forename: Sofia
authors.initials: S
authors.lastname: Merajver
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: Helena
authors.initials: H
authors.lastname: Jernstrom
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Brunet
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000150:complications; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D003278:Contraceptives, Oral, Hormonal