Systematic Review and Meta-Analysis of 16S rRNA and Cancer Microbiome Atlas Datasets to Characterize Microbiota Signatures in Normal Breast, Mastitis and Breast Cancer

The breast tissue microbiome has been increasingly recognized as a potential contributor to breast cancer development and progression. However, inconsistencies in microbial composition across studies have hindered the identification of definitive microbial signatures. To address these gaps, we conducted a systematic review and meta-analysis of 11 studies employing 16S rRNA sequencing to characterize the bacterial microbiome across 1,260 fresh breast tissue samples, including normal, mastitis-affected, benign, cancer-adjacent, and cancerous tissues. We also incorporated microbiome data from The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort to enhance our analyses. Our meta-analysis identified Proteobacteria, Firmicutes, Actinobacteriota, and Bacteroidota as the dominant phyla in breast tissue, with Staphylococcus and Corynebacterium frequently detected across studies. While microbial diversity was similar between cancer and cancer-adjacent tissues, both exhibited lower diversity compared to normal and mastitis-affected tissues. Variability in bacterial genera was observed across primer sets and studies, emphasizing the need for standardized methodologies in microbiome research. Analysis of TCGA-BRCA data confirmed the dominance of Staphylococcus and Corynebacterium, which was associated with breast cancer proliferation-related gene expression programs. Notably, high Staphylococcus abundance was associated with a 4.1-fold increased mortality risk. These findings underscore the potential clinical relevance of the breast microbiome in tumor progression and emphasize the importance of methodological consistency. Future studies to establish causal relationships, elucidate underlying mechanisms, and assess microbiome-targeted interventions are warranted.