In this regard, accumulated evidence has shown recurrent alterations in diverse genes (i.e., TP53, ESR1, PIK3CA, PTEN, CDH1, GATA3, CCND1, FGFR1/2, ERBB2, CDKN2A/2B, MYC and BRCA1/2) as well as dysregulations in various signaling pathways (i.e., hormone receptors, DNA damage repair, PI3K/AKT/mTOR, MAPK/ERK, TGF-β, NFκB, WNT/β-Catenin, Notch, Hippo, and SHH), which are associated with cell survival, proliferation, epithelial-mesenchymal transition (EMT), therapy resistance, immune evasion and tumor immune microenvironment (TIME) alterations in BC (1, 8–19). This evidence concerns the gene ESR1 and breast cancer.