ESR1 and neoplasm: Estrogen receptor alpha (ERα)/estrogen (17-β-estradiol, E2) signaling pathway exerts its various biological functions on normal mammary gland development, breast tumorigenesis, and tumor growth process (1–4). Although anti-estrogen has been widely adopted in ERα-positive breast cancer prevention and treatment (5,6), endocrine therapy resistance finally occurs due to many mechanisms, including depletion of ERα expression, activation of truncated ER isoforms, post-translational modification of ERα, abnormal regulation of ERα coactivators, and increased tyrosine kinase signaling (7–10).