Breast cancer: estrogens as carcinogens

Abstract

The major known risk factors for breast cancer are associated with a prolonged exposure to increased levels of estrogens and their reactive metabolites. The mechanisms through which estrogens contribute to the carcinogenic process are complex. Evidence suggests the involvement of estrogen-receptor-mediated signalling which increases cell proliferation of mammary tissue. Furthermore, the metabolism of estrogens leads to the production of reactive metabolites, which exert genotoxic effects. Considerable inter-individual variability in the metabolic pathways of estrogens is attributed to polymorphisms in the genes encoding for enzymes involved in estrogen metabolism. These person-to-person differences define subpopulations of women with different lifetime exposure to estrogens and/or estrogen metabolites. Assessing these genetic differences is therefore relevant as it may help to identify postmenopausal women who are particularly susceptible to breast cancer if exposed to exogenous hormones by hormone replacement therapy.