Recent advances in understanding the role of chemokines in breast cancer microenvironment remodelling

Breast cancer is the most prevalent malignancy among women worldwide. Chemokines facilitate intercellular communication within the tumor microenvironment and critically influence disease progression. Using the TCGA database, we identify CXCL12, CXCL9, and CCL2 as being among the most aberrantly expressed chemokines in breast cancer, and they might be proposed as important targets for drug design. Notably, the same chemokine exerts context-dependent effects depending on tumor subtypes, metastatic organs (lung, bone, brain, and liver), and disease stages, which causes chemokine-targeted inhibitors to show limited efficacy. We also review the roles of chemokines and their receptors in angiogenesis and immune microenvironment remodeling. Furthermore, we analyze major translational bottlenecks, including target redundancy, context-specificity, acquired resistance, and the lack of predictive biomarkers. This review tries to elucidate the molecular mechanisms linking chemokines and their cognate receptors to breast cancer, and provide a foundation for developing targeted inhibitors－thereby advancing therapeutic strategies in breast cancer.