Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS).
BACKGROUND
Multiparity, young age at first childbirth, and breast-feeding are associated with a reduced risk of breast cancer in the general population. The breast cancer predisposition gene, BRCA1, regulates normal cell differentiation. Because mammary gland cells divide and differentiate during pregnancy, reproductive factors may influence breast cancer risk in BRCA1/2 mutation carriers differently than they do in noncarriers.


METHODS
We performed a retrospective cohort study of 1601 women in the International BRCA1/2 Carrier Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2. Information on reproductive factors was obtained from a questionnaire. At the time of interview 853 subjects were classified with breast cancer. Data were analyzed by using a weighted cohort approach. All statistical tests were two-sided.


RESULTS
There was no statistically significant difference in the risk of breast cancer between parous and nulliparous women. Among parous women, an increasing number of full-term pregnancies was associated with a statistically significant decrease in the risk of breast cancer (Ptrend = .008); risk was reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional birth. This association was the same for carriers of mutations in either BRCA1 or BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation carriers, first childbirth at later ages was associated with an increased risk of breast cancer compared with first childbirth before age 20 years (20-24 years, hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI = 1.02 to 7.07]; > or = 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in BRCA1 mutation carriers, first childbirth at age 30 years or later was associated with a reduced risk of breast cancer compared with first childbirth before age 20 years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted pregnancies (induced abortions or miscarriage) nor history of breast-feeding was statistically significantly associated with the risk of breast cancer.


CONCLUSIONS
BRCA1 and BRCA2 mutation carriers older than 40 years show a similar reduction in breast cancer risk with increasing parity as non-carriers.
Andrieu
Nadine
N
INSERM, Emi00-06, Service de Biostatistique, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. nadine.andrieu@curie.net
Goldgar
David E
DE
Easton
Douglas F
DF
Rookus
Matti
M
Brohet
Richard
R
Antoniou
Antonis C
AC
Peock
Susan
S
Evans
Gareth
G
Eccles
Diana
D
Douglas
Fiona
F
Noguès
Catherine
C
Gauthier-Villars
Marion
M
Chompret
Agnès
A
Van Leeuwen
Flora E
FE
Kluijt
Irma
I
Benitez
Javier
J
Arver
Brita
B
Olah
Edith
E
Chang-Claude
Jenny
J
D000028:Abortion, Induced; D000328:Adult; D000367:Age Factors; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D005060:Europe; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007391:International Cooperation; D008875:Middle Aged; D009154:Mutation; D010298:Parity; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000453:epidemiology* / Q000235:genetics; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors