In ER-positive BC, the activation of CXCR4 signaling has been demonstrated to drive BC cells to an invasive and endocrine therapy-resistant phenotype through the activation of extracellular signal-regulated kinases (ERK) 1/2, p38 mitogen-activated protein kinase (MAPK), and NF-κB pathways and through the enhancement of ER-mediated gene expression [23, 24, 34]. This evidence concerns the gene ESR1 and breast cancer.