ESR1 and breast cancer: The endocrine therapy aims at limiting the growth and survival of ER-positive (ER+) cancers[18] by means of the promotion of ER degradation using specific ER downmodulators (e.g., fulvestrant), the antagonized binding of estrogens with selective ER modulators (SERMs) (e.g., tamoxifen), or blocking estrogen synthesis by aromatase inhibitors (AIs)[19], which are also the elective therapy for post-menopausal women with ER+ BC[20].