Intratumoral Microbiome-Tumor Microenvironment Crosstalk in Breast Cancer Aggressiveness

Breast cancer (BC) remains the most common malignancy among women worldwide, with incidence and mortality rates continuing to rise. Alongside tumor heterogeneity and diverse clinical outcomes, increasing attention has been directed toward the role of the intratumoral microbiome as a regulator of breast tumorigenesis. Recent evidence demonstrates that breast tissue harbors one of the most diverse microbial communities compared with other cancer types, with marked differences between normobiota and malignant tissue. Intratumoral microorganisms are potentially associated with BC progression through multiple mechanisms, including modulation of inflammation, steroid hormone metabolism, and extracellular matrix remodeling. Specific taxa, including Staphylococcus, Bacillus, Fusobacterium, and Paenibacillus, have been associated with tumor aggressiveness, molecular subtypes, and patient prognosis. Moreover, the microbiome actively shapes the tumor microenvironment by altering immune infiltration, inducing resistance to anticancer therapy, and regulating immune checkpoint signaling, including PD-1/PD-L1 pathways. Microbial proteases and bacterial analogs of matrix metalloproteinases further contribute to extracellular matrix degradation and stromal remodeling, enhancing metastatic potential. Despite rapid advances, the clinical utility of intratumoral microbial signatures as predictive biomarkers of BC aggressiveness remains under investigation. Comprehensive characterization of microbial profiles across clinical and molecular subgroups may offer novel diagnostic, prognostic, and therapeutic opportunities in BC management.