Using in vitro assessments and syngeneic immunocompetent murine breast cancer models, we here report potential mechanisms through which the small molecule antagonist of CXCR4, AMD3465, can inhibit breast cancer growth and metastasis, and demonstrate the biologically relevant modulation of oncogenic signaling and tumor microenvironment by AMD3465. The gene discussed is CXCR4; the disease is neoplasm.