title: Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations.
abstract: BACKGROUND
  Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear.
  
  
  METHODS
  Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls.
  
  
  RESULTS
  After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001).
  
  
  CONCLUSIONS
  There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
authors.affiliation: Centre for Genetic Epidemiology, The University of Melbourne, Level 2, 723 Swanston Street, Carlton, Victoria 3053, Australia. j.hopper@unimelb.edu.au.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.forename: Ronald
authors.initials: R
authors.lastname: Balbuena
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ziogas
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: Dee W
authors.initials: DW
authors.lastname: West
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Li
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Margaret R E
authors.initials: MR
authors.lastname: McCredie
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D012307:Risk Factors; D044465:White People
chemical_list: D003276:Contraceptives, Oral