ESR1 and breast neoplasm: Most primary breast tumors are ER+/PR+/HER2-, and patients are treated with surgery, radiation, and endocrine therapies (also referred to as antiestrogen therapies) Endocrine therapies employ aromatase inhibitors (AI), e.g., letrozole, to block the conversion of androgens to estrogens, or tamoxifen (TAM), which is a selective ER modulator (SERM) that competes with estrogens, including estradiol (E2) for binding ER.