Breast Tumour Tissue Subtypes Are Associated with Distinct Microbiome Composition and Functional Profiles

Breast cancer is the most commonly diagnosed cancer in women worldwide and encompasses multiple tumour subtypes that arise from distinct anatomical and histological regions of the breast. Although previous research has shown that the breast microbiome influences tumour development and malignancy, it remains unclear whether microbial composition and function vary across the tissue type of breast tumours and if menopause influences these patterns. Using a previously published 16S rRNA dataset of breast tissue samples (n=71) associated with benign tumours (n=13), malignant tumours (n=45) and healthy tissue (n=23), we grouped around 20 tumour classifications into five broader tissue types to compare diversity metrics, indicator taxa, differential abundance, and predicted metabolic pathways between the tissue types. We found no significant differences (p>0.05) in microbial diversity and composition between pre- and post-menopausal groups. Microbial community composition was significantly dissimilar across tissue categories (p<0.05), supported by distinct indicator taxa in all tissue types except ductal gland epithelium. Connective tissue exhibited higher microbial richness and contained the largest number of indicator genera (n=9). In addition, differential abundance and functional pathway analyses revealed shifts in carbohydrate metabolism that appeared to follow trends linked with tumour severity as determined by prognosis. These findings indicate that the tissue type of breast tumours is associated with differences in microbial composition and predicted functional activity. Distinguishing the tumour micro-environments in the different tissue groups may provide insight into breast cancer development, improve diagnostic tools, and support the development of potential targeted treatments.