ESR1 and breast cancer: Estrogens bind to ERs α/β and strongly stimulate the proliferation of normal mammary epithelial cells and BCs by inducing c-MYC oncogene expression.20–22 Because of the extremely high potential for estrogens to stimulate cellular proliferation, ER antagonists are currently the first-line therapy for patients with ER+ BC.23 Ligand-activated ERs bind to enhancers, leading to the transient transcription of multiple genes.24–27 17β-Estra-diol (E2) exposure causes the recruitment of the FoxA1 transcription factor to genomic DNA independent of ERs.