Microbiome-Driven Mechanisms in Breast Cancer: Emerging Evidence From Gut Microbial Signatures to Therapeutic...

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, and increasing evidence indicates that the gut microbiome plays a significant role in tumor initiation, progression, and therapeutic response. Microbial dysbiosis and altered metabolite production have been associated with systemic inflammation, estrogen metabolism, immune regulation, and metabolic reprogramming, all of which contribute to breast cancer biology. This review summarizes current preclinical and clinical evidence describing the gut-breast cancer axis and its mechanistic and translational relevance. The review focuses on four major pathways through which gut microbiota may influence breast cancer development and treatment outcomes: immune modulation, estrobolome-mediated estrogen recycling, chronic inflammatory signaling, and microbial metabolite-driven epigenetic and metabolic regulation. Evidence from experimental models and human studies demonstrates that alterations in microbial diversity and enrichment of proinflammatory taxa are associated with tumor progression, subtype-specific biology, and variability in therapeutic response. Emerging findings further indicate that microbiome composition can influence the efficacy and toxicity of chemotherapy, endocrine therapy, radiotherapy, and immunotherapy, highlighting the potential of microbiome-informed precision oncology strategies. In addition, this review discusses current advances in microbiome-targeted interventions including probiotics, dietary modulation, postbiotics, and fecal microbiota transplantation. Despite promising translational potential, significant challenges remain regarding mechanistic validation, standardization of microbiome profiling, reproducibility across cohorts, and clinical implementation. Future research integrating longitudinal multiomics approaches, functional validation studies, and personalized microbiome-based therapeutic strategies may facilitate the development of clinically actionable microbiome interventions for breast cancer management.