Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Cancer Epidemiology, Biomarkers and Prevention Year : 2015

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

Catherine Nogues
Olivier Caron
  • Function : Author
Julie Tinat
  • Function : Author

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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inserm-01990932 , version 1 (23-01-2019)

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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, 2015, 24 (4), pp.698-707. ⟨10.1158/1055-9965.epi-14-0884⟩. ⟨inserm-01990932⟩
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