Dissecting the Non-Immune Tumor Microenvironment in Triple-Negative Breast Cancer: Molecular Subtype-Specific...

Triple-Negative Breast Cancer (TNBC) encompasses a biologically heterogeneous group of tumors, which can be classified into distinct molecular subtypes, namely basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR), with unique clinical and pathological characteristics. While immune features of these subtypes have been extensively characterized, the integration of non-immune stromal and structural components into our understanding of TNBC biology is only now being fully recognized. This narrative review synthesizes current evidence regarding differences in the non-immune microenvironment across TNBC molecular subtypes, with a focus on cancer-associated fibroblasts (CAFs), vascular features, extracellular matrix (ECM) dynamics, and epithelial-mesenchymal transition (EMT), along with metabolic-hypoxic reprogramming. Data from several studies are integrated to highlight subtype-specific signatures. Differences in stromal architecture and metabolic adaptations, potentially reflecting the underlying molecular heterogeneity, may hold prognostic or predictive significance and could inform personalized therapeutic strategies targeting the tumor-stroma interface.