ESR1 and cancer: One of the most devastating features of solid tumors is distant spreading or stage IV cancer metastasis, predicting unfavorable overall survival for all breast cancers6, especially estrogen receptor (ER) negative breast cancers, such as triple-negative breast cancer (TNBC) which lacks expression of ER, progesterone receptor, and epidermal growth factor receptor 2 (HER2)7–9 with the lowest 5-year survival rate (~10%) after metastasis to the lungs, brain, and liver10, followed by HER2-positive breast cancer (~40%)6.