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Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers

Julie Lecarpentier 1 Catherine Nogues 2 Emmanuelle Mouret-Fourme 2 Bruno Buecher 3 Marion Gauthier-Villars 3 Dominique Stoppa-Lyonnet 4 Valérie Bonadona 5, 6 Jean-Pierre Fricker 7 Pascaline Berthet 8 Olivier Caron 9 Isabelle Coupier 10, 11 Pascal Pujol 10, 11 Laurence Faivre 12 Paul Gesta 13 François Eisinger 14, 15 Véronique Mari 15 Laurence Gladieff 16, 17 Alain Lortholary 18 Elisabeth Luporsi 19, 20 Dominique Leroux 21 Laurence Venat-Bouvet 22 Christine M Maugard 23 Chrystelle Colas 24 Julie Tinat 25 Christine Lasset 6 Nadine Andrieu 1, * 
Abstract : BACKGROUND:Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.METHODS:We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.RESULTS:We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.CONCLUSIONS:As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones.IMPACT:Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers.
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Submitted on : Wednesday, January 23, 2019 - 3:00:46 PM
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Julie Lecarpentier, Catherine Nogues, Emmanuelle Mouret-Fourme, Bruno Buecher, Marion Gauthier-Villars, et al.. Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers. Cancer Epidemiology, Biomarkers and Prevention, American Association for Cancer Research, 2015, 24 (4), pp.698-707. ⟨10.1158/1055-9965.epi-14-0884⟩. ⟨inserm-01990932⟩



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