The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.

Breast cancer metastasis remains the leading cause of cancer-related mortality and is closely linked to immune evasion and tumor microenvironment (TME) remodeling. Emerging evidence suggests that intratumoral microbiota (ITM), typically low in biomass and predominantly intracellular, may be associated with tumor progression. This review summarizes the compositional features of ITM and their potential roles in metastasis, including epithelial-mesenchymal transition (EMT), circulating tumor cell (CTC) survival, pre-metastatic niche formation, and distant colonization. Mechanistically, ITM may influence these processes through immune-related signaling pathways (e.g., PRR-mediated cascades) and modulation of immune cell function. However, current evidence is largely derived from preclinical or correlative studies, and causal roles in human breast cancer remain unproven. Methodological challenges associated with low biomass further complicate interpretation. We also discuss microbiota-targeted strategies, including probiotics, antibiotics, and fecal microbiota transplantation, which remain experimental. Future studies using rigorous methodologies and longitudinal human data are required to clarify the role of ITM and its clinical potential.