ESR1 and breast cancer: Estrogen receptor-targeted therapy for breast cancer was first used in 1896 by Beatson (3) and currently, at least six distinct therapeutic modalities are established, namely selective ER modulators (SERMs) (tamoxifen, raloxifene, and toremifene), selective ER down-regulators (SERDs), aromatase inhibitors (anastrozole, letrozole, and exemestane), mammalian target of rapamycin inhibitors in combination with aromatase inhibitors, and cyclin-dependent kinases 4 and 6 inhibitors in combination with aromatase inhibitors and cyclin-dependent kinases 4 and 6 inhibitors in combination with SERDs (4).