ESR1 and breast cancer: Estrogen’s association with BC operates by both hormonal ER-mediated stimulation of breast cell proliferation, with enhanced chances of mutations, and estradiol’s genotoxic metabolites that generate oxygen free radicals and alterations, initiating DNA mutagenic processes (Cavalieri and Rogan, 2014); both mechanisms are reduced by a variety of estrogen inhibitors (Santen et al., 2015).