Intra-tumoral microbial heterogeneity of breast cancer: roles in tumorigenesis, therapeutic responses, and future directions

Recent advances in microbiome research have revealed that tumor-resident microbiota are not passive bystanders but active contributors to the progression of breast cancer. Similar to the well-characterized gut-breast microbiota axis, emerging evidence points to intricate interactions between intra-tumoral microbiota and breast cancer with implications for carcinogenesis, therapeutic response, and future directions. Intra-tumoral microbes have been shown to initiate inflammation, modulate tumor microenvironment, alter drug metabolism, and produce bioactive metabolites that influence tumor cell proliferation, apoptosis, and epithelial-mesenchymal transition. Distinct microbial signatures have been associated with specific molecular subtypes of breast cancer and may serve as predictive biomarkers for prognosis. Furthermore, dysbiosis within the tumor-resident microbiota has been linked to the development of treatment resistance, including chemotherapy, immunotherapy, and endocrine therapy. Preclinical studies support the feasibility of modulating the microbiota via using antibiotics, probiotics, fecal microbiota transplantation, or bacteriophage-based strategies to enhance antitumor efficacy and overcome resistance. This review summarizes current knowledge on the biological roles of tumor-resident microbiota in breast cancer, highlights subtype-specific microbial patterns and host-microbe interactions, and explores microbiota-targeted interventions as promising adjuncts in overcoming drug resistance.