title: Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group.
abstract: PURPOSE Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/2 carriers. PATIENTS AND METHODS In the International BRCA1/2 Carrier Cohort study (IBCCS), a retrospective cohort of 1,593 BRCA1/2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/2 mutation carriers who ever used oral contraceptives (adjusted hazard ratio [HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full-term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers (4 or more years of use before first full-term pregnancy: HR = 1.49 [95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [95% CI, 1.21 to 5.49] for BRCA2 carriers). CONCLUSION No evidence was found among BRCA1/2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full-term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.
authors.affiliation: Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Brohet
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: Margaret
authors.initials: M
authors.lastname: Cook
authors.forename: Carol
authors.initials: C
authors.lastname: Chu
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldes
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Matti A
authors.initials: MA
authors.lastname: Rookus
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D003276:Contraceptives, Oral