ESR1 and breast cancer: Mechanisms demonstrated that downregulation of ERα and GPER [44], selectively downregulation of the mRNA and enzymatic activity levels of steroid sulfatase [45], as well as specifically inhibition of pyruvate kinase-M2 in MCF-7 and many drug resistance cancer cells [46, 47], are the mainly involved molecular mechanisms for SKO induced breast cancer cell necrosis and apoptosis, which is significant different from the disclosed mechanisms of SKO induced cytotoxicity in MDA-MB-231 cell lines in our study.