ESR1 and breast cancer: Most early-stage breast cancers are estrogen receptor α—positive and epidermal growth factor receptor 2 (EGFR2, HER2) negative [3], and are treated with antiestrogens such as tamoxifen and/or aromatase inhibitors (e.g., anastrozole), which block the ERα-mediated function and inhibit 17β-estradiol synthesis, respectively [4].