Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers.
It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
Familial Breast Cancer Unit, Women's College Research Institute, 790 Bay Street, Room 750, Toronto, ON, M5G 1N8, Canada.
Joanne
J
Kotsopoulos
Jan
J
Lubinski
Pal
P
Moller
Henry T
HT
Lynch
Christian F
CF
Singer
Charis
C
Eng
Susan L
SL
Neuhausen
Beth
B
Karlan
Charmaine
C
Kim-Sing
Tomasz
T
Huzarski
Jacek
J
Gronwald
Jeanna
J
McCuaig
Leigha
L
Senter
Nadine
N
Tung
Parviz
P
Ghadirian
Andrea
A
Eisen
Dawna
D
Gilchrist
Joanne L
JL
Blum
Dana
D
Zakalik
Tuya
T
Pal
Ping
P
Sun
Steven A
SA
Narod
D000328:Adult; D000367:Age Factors; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D003276:Contraceptives, Oral