title: Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS).
abstract: 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.
authors.affiliation: INSERM, Emi00-06, Service de Biostatistique, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. nadine.andrieu@curie.net
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Matti
authors.initials: M
authors.lastname: Rookus
authors.forename: Richard
authors.initials: R
authors.lastname: Brohet
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Fiona
authors.initials: F
authors.lastname: Douglas
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Flora E
authors.initials: FE
authors.lastname: Van Leeuwen
authors.forename: Irma
authors.initials: I
authors.lastname: Kluijt
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.forename: Brita
authors.initials: B
authors.lastname: Arver
authors.forename: Edith
authors.initials: E
authors.lastname: Olah
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
mesh_terms: 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