ESR1 and metastatic neoplasm: The experiments were performed in cell lines modeling either primary ERα+ breast tumors sensitive to 4OH-Tam (i.e., MCF-7 and ZR-75-1 cells) or modeling metastatic tumors with acquired resistance to 4OH-Tam (i.e., 4OH-Tam resistant MCF-7 cells–Tam Res) [22] or with genetic resistance to endocrine therapy drugs (i.e., MCF-7 cells CRISPR/CAS9 engineered to express the Y537S ERα point mutant-Y537S) [2,15].