Enhanced drug efflux, alteration of drug targets (e.g., estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)), increased DNA damage repair (DDR), activated cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT), defective cell cycle control, apoptosis/survival pathways dysregulation, and the oncogenic signals within the tumor microenvironment (TME) have been extensively reviewed in association with the development of drug resistance in BC [10,11,12]. Here, ESR1 is linked to cancer.