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The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Mary Beth Terry 1 Yuyan Liao 1 Karin Kast 2 Antonis C. Antoniou 3 Jasmine Mcdonald Thea Mooij Christoph Engel 4 Catherine Noguès 5 Bruno Buecher 6 Veronique Mari 7 Jessica Moretta-Serra Laurence Gladieff 8 Elisabeth Luporsi 9 Daniel Barrowdale 3 Debra Frost 3 Alex Henderson 10 Carole Brewer 11 D Gareth Evans 12 Diana Eccles 13 Jackie Cook 14 Kai-Ren Ong 15 Louise Izatt 16 Munaza Ahmed 12 Patrick Morrison 17 Charlotte Dommering 18 Jan Oosterwijk 19 Margreet Ausems 20 Mieke Kriege 21 Saundra Buys 22 Irene Andrulis 23 Esther M. John 24 Mary B. Daly 25 Michael Friedlander 26 Sue Anne Mclachlan Ana Osorio 27 Trinidad Caldés 28 Anna Jakubowska 29 Jacques Simard 30 Christian Singer 31 Yen Tan Edith Olah 32 Marie Navratilova Lenka Foretova 33 Anne-Marie Gerdes 34 Marie-José Roos-Blom Brita Arver 35 Håkan Olsson 36 Rita Schmutzler 37 John Hopper 38 Flora E. van Leeuwen 39 David E. Goldgar 40 Roger L Milne 41 Douglas Easton 42 Matti A. Rookus 43 Nadine N. Andrieu 44 
1 Department of Epidemiology [Columbia University]
Columbia University [New York], Columbia Mailman School of Public Health
Abstract : BACKGROUND: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. METHODS: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. RESULTS: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). CONCLUSIONS: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
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Mary Beth Terry, Yuyan Liao, Karin Kast, Antonis C. Antoniou, Jasmine Mcdonald, et al.. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations. JNCI Cancer Spectrum, Oxford University Press, 2018, 2 (4), pky078. ⟨10.1093/jncics/pky078⟩. ⟨inserm-02438434⟩



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