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- Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers
Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers
Auteurs
Julie Lecarpentier, Catherine Noguès, Emmanuelle Mouret-Fourme, Bruno Buecher, Marion Gauthier-Villars, Dominique Stoppa-Lyonnet, Valérie Bonadona, Jean-Pierre Fricker, Pascaline Berthet, Olivier Caron, Isabelle Coupier, Pascal Pujol, Laurence Faivre, Paul Gesta, François Eisinger, Véronique Mari, Laurence Gladieff, Alain Lortholary, Elisabeth Luporsi, Dominique Leroux, Laurence Venat-Bouvet, Christine M. Maugard, Chrystelle Colas, Julie Tinat, Christine Lasset, Nadine Andrieu
Résumé
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. Cancer Epidemiol Biomarkers Prev; 24(4); 698–707. ©2015 AACR.