Key players in the breast cancer microenvironment: From fibroblasts to immune cells

Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women. Beyond tumor cells, the tumor microenvironment (TME) also plays an important role in cancer progression, therapy resistance, and metastasis. The TME is a complex ecosystem consisting of stromal and immune cells, extracellular matrix (ECM), and various signaling molecules that dynamically interact with tumor cells. Cancer-associated fibroblasts remodel the ECM and secrete growth factors that promote tumor growth and invasion. Immune cells, such as tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, often contribute to an immunosuppressive environment that hinders anti-tumor immune responses. The ECM provides structural support and acts as a reservoir for signaling molecules that influence cancer cell behavior. These components evolve together with tumor cells, facilitating immune evasion, therapy resistance, and epithelial-to-mesenchymal transition, which promotes metastasis. Understanding these interactions is necessary to develop novel therapeutic strategies that target both tumor and microenvironmental components. This minireview highlights the key stromal and immune elements within the breast cancer microenvironment, discussing their individual and collective roles in tumor progression and clinical outcomes, while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.