Distinct Microbial Signatures Associated With Different Breast Cancer Types

Abstract

A dysbiotic microbiome can potentially contribute to the pathogenesis of many different diseases including cancer. Breast cancer is the second leading cause of cancer death in women. Thus, we investigated the diversity of the microbiome in the four major types of breast cancer: endocrine receptor (ER) positive, triple positive, Her2 positive and triple negative breast cancers. Using a whole genome and transcriptome amplification and a pan-pathogen microarray (PathoChip) strategy, we detected unique and common viral, bacterial, fungal and parasitic signatures for each of the breast cancer types. These were validated by PCR and Sanger sequencing. Hierarchical cluster analysis of the breast cancer samples, based on their detected microbial signatures, showed distinct patterns for the triple negative and triple positive samples, while the ER positive and Her2 positive samples shared similar microbial signatures. These signatures, unique or common to the different breast cancer types, provide a new line of investigation to gain further insights into prognosis, treatment strategies and clinical outcome, as well as better understanding of the role of the micro-organisms in the development and progression of breast cancer.

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

“…1 The largest study to examine microbes and BC was from The Cancer Genome Atlas (TCGA) wherein Proteobacteria, Actinobacteria, and Firmicutes were shown as the most abundant phyla in breast tumors, which is consistent with our work and others, and reminiscent of the gut. 1,11,14,18,21,168,[172][173][174][175][176]180,181 We detected dysbiosis in breast tumors and tumor-adjacent breast tissue compared to normal tissue from healthy subjects. Recall that Ruminococcus is high in the gut of BC patients 11 and reduced by Mediterranean diet in the mammary glands of monkeys.…”

“…167 Examination of the local microbiome in BC compared to normal tumor-adjacent or normal mammary gland has revealed interesting alterations. 11,14,168,[172][173][174][175][176] The Western diet is associated with obesity and poor tumor outcomes. 177 Cook et al showed for the first time that Mediterranean vs Western diet could alter mammary gland microbes, specifically increasing Lactobacillus by 10-fold and reducing Ruminococcus in the mammary gland of non-human primates.…”

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

“…Moreover, a report compared four major breast cancer types with respect to their microbial signatures and described differences in their bacterial, viral, fungal, and parasitic compositions. For instance, two breast cancer subtypes (triple-negative and triple-positive) were remarkably distinct from each other, exhibiting very different microbial patterns [31]. Besides that, microbiome compositions were related with prostate health and disease.…”

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

“…Recent advances in the sensitive detection of pathogens revealed that tumors harbor a diverse set of bacteria, viruses and fungi [51,52], a community, which, in analogy to the "microbiome" in the gut, has been labeled the "oncobiome" [53]. Sequencing of bacterial 16S RNA as a species-specific genetic fingerprint identified several hundred different bacterial species in each tumor [54].…”