The chemokine (C-C motif) ligand 2 (CCL2) secreted by tumor-associated macrophages activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the tumor microenvironment (TME), suggesting that CCL2 and tumor-associated macrophages may be novel therapeutic targets for patients with endocrine-resistant breast cancer (112). This evidence concerns the gene AKT1 and breast cancer.