© The Author 2006. Published by Oxford University Press.
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Pregnancies, Breast-Feeding, and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study (IBCCS)
Affiliations of authors: INSERM, Emi00–06, Services de Biostatistiques, Institut Curie, France (NA); International Agency for Research on Cancer, Lyon, France (DEG); Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (DFE, ACA, SP); The Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands (MR, RB, FEVL, IK); Manchester Regional Genetics Service, Manchester, United Kingdom (GE); Wessex Clinical Genetics Service, Southampton, United Kingdom (DE); Northern Clinical Genetics Service, Newcastle, United Kingdom (FD); Centre René Huguenin, Saint Cloud, France (CN); Institut Curie, Service d'Oncogénétique, Paris, France (MGV); Institut Gustave Roussy, Villejuif, France (AC); Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Madrid, Spain (JB); Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden (BA); National Institute of Oncology, Budapest, Hungary (EO); Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany (JCC)
Correspondence to: Nadine Andrieu, PhD, INSERM, Emi00–06, Services de Biostatistiques, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France (e-mail: nadine.andrieu{at}curie.net) or Jenny Chang-Claude, PhD, Division of Clinical Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (e-mail: j.chang-claude{at}dkfz-heidelberg.de).
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]; 
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.
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Correspondence about this Article
- Re: Pregnancies, Breastfeeding, and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study (IBCCS)
- Laetitia Huiart and Marie-Pierre Sylvestre
J Natl Cancer Inst 2007 99: 1130-1131.[Extract] [Full Text] [PDF]
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