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.
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: Antonis C Antoniou; David E Goldgar; Nadine Andrieu; Jenny Chang-Claude; Richard Brohet; Matti A Rookus; Douglas F Easton Journal: Genet Epidemiol Date: 2005-07 Impact factor: 2.135
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Authors: Antonis C Antoniou; Olga M Sinilnikova; Jacques Simard; Mélanie Léoné; Martine Dumont; Susan L Neuhausen; Jeffery P Struewing; Dominique Stoppa-Lyonnet; Laure Barjhoux; David J Hughes; Isabelle Coupier; Muriel Belotti; Christine Lasset; Valérie Bonadona; Yves-Jean Bignon; Timothy R Rebbeck; Theresa Wagner; Henry T Lynch; Susan M Domchek; Katherine L Nathanson; Judy E Garber; Jeffrey Weitzel; Steven A Narod; Gail Tomlinson; Olufunmilayo I Olopade; Andrew Godwin; Claudine Isaacs; Anna Jakubowska; Jan Lubinski; Jacek Gronwald; Bohdan Górski; Tomasz Byrski; Tomasz Huzarski; Susan Peock; Margaret Cook; Caroline Baynes; Alexandra Murray; Mark Rogers; Peter A Daly; Huw Dorkins; Rita K Schmutzler; Beatrix Versmold; Christoph Engel; Alfons Meindl; Norbert Arnold; Dieter Niederacher; Helmut Deissler; Amanda B Spurdle; Xiaoqing Chen; Nicola Waddell; Nicole Cloonan; Tomas Kirchhoff; Kenneth Offit; Eitan Friedman; Bella Kaufmann; Yael Laitman; Gilli Galore; Gad Rennert; Flavio Lejbkowicz; Leon Raskin; Irene L Andrulis; Eduard Ilyushik; Hilmi Ozcelik; Peter Devilee; Maaike P G Vreeswijk; Mark H Greene; Sheila A Prindiville; Ana Osorio; Javier Benitez; Michal Zikan; Csilla I Szabo; Outi Kilpivaara; Heli Nevanlinna; Ute Hamann; Francine Durocher; Adalgeir Arason; Fergus J Couch; Douglas F Easton; Georgia Chenevix-Trench Journal: Am J Hum Genet Date: 2007-10-16 Impact factor: 11.025