Number of Pregnancies Influences Breast Cancer Risk for Women with BRCA Mutations

Risk of breast cancer declined for women with BRCA1 gene and more than one pregnancy

March 11, 2019

Researchers at Columbia University Mailman School of Public Health and the Institut National de la Santé et de la Recherche Médicale in Paris confirm the lower risk of breast cancer from multiple pregnancies and from breast feeding seen in average risk women extends to those at the highest risk of breast cancer, according to the largest prospective study of BRCA1 and BRCA2 mutations carriers to date. Women with BRCA1 mutations who had two, three or four or more full-term pregnancies were at 21 percent, 30 percent, and 50 percent decrease risk of breast cancer compared to women with a single full-term pregnancy. Breastfeeding also reduced risk in BRCA1 mutation carriers.  The results are published online in the Journal of the National Cancer Institute Cancer Spectrum.
In contrast, women with BRCA2 mutations did not have a decrease in risk from multiple pregnancies except if they had four or more pregnancies.  Women with BRCA1 mutations who had only one full-term pregnancy were at an increased risk of breast cancer as were women with BRCA2 mutations who had fewer than four pregnancies.
“What we have learned is that timing really matters for many risk factors and the dual effect of pregnancy we see in non-mutation carriers with a long term protection but short term increase following a pregnancy may not extend to all women with BRCA1 and BRCA2 mutations as the short-term increase and long-term protection may relate much more to the timing of when these pregnancies occur,” said lead author Mary Beth Terry, PhD, Professor of Epidemiology and Environmental Health Sciences at the Mailman School of Public Health at Columbia University and the Herbert Irving Comprehensive Cancer Center.  
“Moreover, the hormonal upheaval that occurs during the first pregnancy may have a more or less important impact on the risk of breast cancer depending on whether the first pregnancy occurs during periods of life at higher risk of developing a breast cancer or at less high risk, periods shifted by about ten years between BRCA2  and BRCA1 mutation carriers, with a later peak for BRCA2 mutation carriers,“ said senior author Nadine Andrieu, PhD, Director of research at the Institut National de la Santé et de la Recherche Médicale and at the Institut Curie, Paris, France.
The study followed 5,707 BRCA1 and 3,535 BRCA2 mutation carriers using a retrospective cohort analysis and 2,276 BRCA1 and 1,610 BRCA2 mutation carrier.  The cohort known as IBCCS (International BRCA1/2 Carrier Cohort Study) includes data from 21 national or center-based prospective follow-up studies whose the national EMBRACE cohort from UK, the national GENEPSO cohort from FR and the national HEBON cohort from NL, the Kathleen Cuningham Foundation Constortium for Research into Familial Breast Cancer Followup Study, and the Breast Cancer Family Registry.   
Co-authors and their affiliated institutions can be found in the paper, “The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations.”
The research was supported with funding from the National Cancer Institute (NCI), NIH, DHHS -USA, Cancer Research – UK, the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, the Australian National Breast Cancer Foundation, the National Health and Medical Research Council, the Queensland Cancer Fund, and the Cancer Foundation of Western Australia, Hungarian Research Grants ,the Norwegian EEA Financial Mechanism, the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant, the Spanish Ministry of Economy and Competitiveness (MINECO), the Spanish Research Network on Rare diseases (CIBERER), the Canadian Institutes of Health Research, the Ministry of Economic Development, Innovation and Export Trade, the Ministère de l’Économie, de la Science et de l' Innovation du Québec, and The Quebec Breast Cancer Foundation, the German Cancer Research Center (DKFZ), the German Cancer Aid, the Fondation de France, the Ligue Nationale Contre le Cancer and Institut National du Cancer –FR,  European Regional Development FEDER –SP, the Dutch Cancer Society, the Netherlands Organisation of Scientific Research, the Pink Ribbon- NL and the European ERA-NET TRANSAN JTC 2012 Cancer 12-054.