The human microbiome reshapes the breast cancer immune-metabolic-hormonal microenvironment

Beyond established risk factors such as genetics and hormones, the human microbiome has emerged as a pivotal player in breast cancer pathogenesis. This review delineates the technological evolution in breast microbiome research, spanning traditional culture methods to high-throughput sequencing and cutting-edge spatial omics. We elucidate the role of the gut-breast axis in modulating breast cancer development through its influence on estrogen metabolism, immune responses, and microbial metabolites. Furthermore, we analyze the distinctive compositional features of the intratumoral microbiota and their dual, context-dependent roles in promoting invasion, inducing immunosuppression, and driving metabolic reprogramming within the tumor microenvironment. Novel microbiome-based therapeutic strategies, including targeted microbiota depletion, engineered microbial therapeutics, and dietary interventions, are summarized. Finally, we discuss the translational potential of microbiome research in refining breast cancer risk prediction, evaluating treatment responses, and advancing personalized prevention and treatment strategies, ultimately contributing to improved patient outcomes.