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.
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.
Brohet
Richard M
RM
Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands.
Goldgar
David E
DE
Easton
Douglas F
DF
Antoniou
Antonis C
AC
Andrieu
Nadine
N
Chang-Claude
Jenny
J
Peock
Susan
S
Eeles
Rosalind A
RA
Cook
Margaret
M
Chu
Carol
C
Noguès
Catherine
C
Lasset
Christine
C
Berthet
Pascaline
P
Meijers-Heijboer
Hanne
H
Gerdes
Anne-Marie
AM
Olsson
Håkan
H
Caldes
Trinidad
T
van Leeuwen
Flora E
FE
Rookus
Matti A
MA
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
D003276:Contraceptives, Oral