ESR1 and breast cancer: Tamoxifen and third-generation aromatase inhibitors (AIs), such as anastrozole, exemestane, and letrozole are established first-line endocrine therapies for the treatment of postmenopausal women with estrogen receptor (ER) –positive, advanced breast cancer.1–3 Given the high prevalence of resistance to AI therapy, multiple treatment options with distinct mechanisms of action are desirable.4