Role of Biological Mediators of Tumor-Associated Macrophages in Breast Cancer Progression

Background: Breast cancer (BRCA) has become the most common cancer worldwide. The tumor microenvironment (TME) in the breast exerts a crucial role in promoting BRCA initiation, progression, and metastasis. Tumor-associated macrophages (TAMs) are the primary component of tumor-infiltrating immune cells through biological mediators that convert TME into malignant tumors. Combinations of these biological mediators can promote tumor growth, metastasis, angiogenesis, and immune suppression and limit the anti-tumor activity of conventional chemotherapy and radiotherapy. Objectives: The present study aimed to highlight the functions of several biological mediators in the breast thatgenerate TME into malignant tumors. Furthermore, this review offers a rationale for TAM-targeted therapy as a novel treatment strategy for BRCA. Results: This review emphasizes TAM-associated biological mediators of TME, viz., cancer- associated fibroblasts, endothelial cells, adipocytes, tumor-derived exosomes, extracellular matrix, and other immune cells, which facilitate TME in malignant tumors. Evidence suggests that the increased infiltration of TAMs and elevated expression of TAMrelated genes are associated with a poor prognosis of BRCA. Based on these findings, TAM-targeted therapeutic strategies, including inhibitors of CSF-1/CSF-1R, CCL2/CCR2, CCL5-CCR5, bisphosphonate, nanoparticle, and exosomal-targeted delivery have been developed, and are currently being employed in intervention trials. Conclusion: This review concludes the roles of biological mediators of TME that interact with TAMs in BRCA, providing a rationale for TAM-targeted therapy as a novel treatment approach for BRCA.