Abstract
It is increasingly thought that part of human susceptibility to cancer is the result of evolutionary mismatches: our ancestors evolved cancer suppression mechanisms in a world largely different from our modern environments. In that context, it has been shown in cohorts from general Western populations that reproductive traits modulate breast cancer risk. Overall, the more menses women experience, the more at risk they are to develop postmenopausal breast cancer. This points towards an evolutionary mismatch but brings the question whether the reproductive pattern also modulates the breast cancer risk in menopausal women at high familial risk. We thus studied the influence of menses on breast cancer risk in a case-control study of 90 postmenopausal women (including BRCA1/2 and non BRCA1/2) nested within a cohort at high familial risk. We tested the association of the lifetime number of menses and the number of menses before first full-term pregnancy with postmenopausal breast cancer risk using Cox survival models. We showed that the total lifetime number of menses was significantly associated with postmenopausal breast cancer risk and associated with a quicker onset of breast cancer after menopause. Those results align with similar studies lead in general cohorts and suggest that the reproductive pattern modulates the familial risk of developing breast cancer after menopause. Altogether, those results impact how we envision breast cancer prevention and call for more research on how ecological and genetic factors shape breast cancer risk.