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Background: Stromal and immune cell composition alterations in benign breast tissue associate with future cancer risk. Pilot data suggest the innate microbiome of normal breast tissue differs between women with and without breast cancer. Microbiome alterations might explain tissue microenvironment variations associated with disease status., Methods: Prospectively-collected sterile normal breast tissues from women with benign (n=16) or malignant (n=17) disease underwent 16SrRNA sequencing with Illumina MiSeq and Hybrid-denovo pipeline processing. Breast tissue was scored for fibrosis and fat percentages and immune cell infiltrates (lobulitis) classified as absent/mild/moderate/severe. Alpha and beta diversity were calculated on rarefied OTU data and associations analyzed with multiple linear regression and PERMANOVA., Results: Breast tissue stromal fat% was lower and fibrosis% higher in benign disease versus cancer (median 30% versus 60%, p=0.01, 70% versus 30%, p=0.002, respectively). The microbiome varied with stromal composition. Alpha diversity (Chao1) correlated with fat% (r=0.38, p=0.02) and fibrosis% (r=-0.32, p=0.05) and associated with different microbial populations as indicated by beta diversity metrics (weighted UniFrac, p=0.08, fat%, p=0.07, fibrosis%). Permutation testing with FDR control revealed taxa differences for fat% in Firmicutes, Bacilli, Bacillales, Staphylococcaceae and genus Staphylococcus, and fibrosis% in Firmicutes, Spirochaetes, Bacilli, Bacillales, Spirochaetales, Proteobacteria RF32, Sphingomonadales, Staphylococcaceae, and genera Clostridium, Staphylococcus, Spirochaetes, Actinobacteria Adlercreutzia. Moderate/severe lobulitis was more common in cancer (73%) than benign disease (13%), p=0.003, but no significant microbial associations were seen., Conclusion: These data suggest a link between breast tissue stromal alterations and its microbiome, further supporting a connection between the breast tissue microenvironment and breast cancer., (Copyright © 2022. Published by Elsevier Inc.)

The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort. Our objective was to characterize the microbiota and associate the microbiota with the tumor expression profiles, for 668 breast tumor tissues and 72 non-cancerous adjacent tissues. The prominent presence of Proteobacteria was increased in the tumor tissues and conversely Actinobacteria abundance increase in non-cancerous adjacent tissues. Further, geneset enrichment suggests Listeria spp to be associated with the expression profiles of genes involved with epithelial to mesenchymal transitions. Moreover, evidence suggests H. influenza may reside in the surrounding stromal material and was significantly associated with the proliferative pathways: G2M checkpoint, E2F transcription factors, and mitotic spindle assembly. In summary, further unraveling this complicated interplay should enable us to better diagnose and treat breast cancer patients.