Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
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.
Narod
Steven A
SA
The Centre for Research on Women's Health, University of Toronto, 790 Bay Street, Toronto, Ontario M5G 1N8, Canada. steven.narod@swchsc.on.ca
Dubé
Marie-Pierre
MP
Klijn
Jan
J
Lubinski
Jan
J
Lynch
Henry T
HT
Ghadirian
Parviz
P
Provencher
Diane
D
Heimdal
Ketil
K
Moller
Pal
P
Robson
Mark
M
Offit
Kenneth
K
Isaacs
Claudine
C
Weber
Barbara
B
Friedman
Eitan
E
Gershoni-Baruch
Ruth
R
Rennert
Gad
G
Pasini
Barbara
B
Wagner
Theresa
T
Daly
Mary
M
Garber
Judy E
JE
Neuhausen
Susan L
SL
Ainsworth
Peter
P
Olsson
Hakan
H
Evans
Gareth
G
Osborne
Michael
M
Couch
Fergus
F
Foulkes
William D
WD
Warner
Ellen
E
Kim-Sing
Charmaine
C
Olopade
Olufunmilayo
O
Tung
Nadine
N
Saal
Howard M
HM
Weitzel
Jeffrey
J
Merajver
Sofia
S
Gauthier-Villars
Marion
M
Jernstrom
Helena
H
Sun
Ping
P
Brunet
Jean-Sebastien
JS
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
D003278:Contraceptives, Oral, Hormonal