Unraveling the microbiome’s role in breast cancer progression and treatment response

Abstract

The human microbiome, encompassing microbial communities in the gut and breast tissue, has emerged as a critical modulator of breast cancer (BC) initiation, progression, and treatment response. This review synthesizes current evidence on the microbiome’s role in BC, highlighting its influence on tumorigenesis, tumor microenvironment (TME), and therapeutic outcomes. Breast cancer, the most prevalent malignancy among women globally, exhibits significant heterogeneity across its molecular subtype’s hormone receptor-positive, HER2-enriched, and triple-negative—each with distinct clinical challenges. Recent studies reveal that microbial dysbiosis in the gut and breast tissue can drive oncogenesis through mechanisms such as immune modulation, estrogen metabolism, and inflammation. Gut microbes, via the “estrobolome,” regulate circulating estrogen levels, impacting hormone-driven BC, while breast tissue microbiota contributes to local inflammation and DNA damage, promoting tumor progression. Specific microbial taxa, including Bacillus, Staphylococcus, and Escherichia coli, are enriched in BC patients, whereas beneficial species like Lactobacillus and Bifidobacterium are diminished. The microbiome also influences treatment efficacy, with gut microbial diversity linked to enhanced chemotherapy and immunotherapy responses, while antibiotic-induced dysbiosis may impair outcomes. Emerging research suggests microbiome signatures as potential biomarkers for predicting therapeutic success, with Akkermansia muciniphila and short-chain fatty acids showing promise in enhancing anti-tumor immunity. Probiotics, prebiotics, and fecal microbiota transplantation offerel therapeutic avenues, though challenges such as standardization, interindividual variability, and safety concerns remain. Integrating multi-omics and machine learning could elucidate microbiome-host interactions, paving the way for precision oncology. This review underscores the transformative potential of microbiome-based diagnostics and interventions in improving BC management, emphasizing the need for large-scale, longitudinal studies to validate these findings and address existing research gaps.