Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients

Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, beta-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC. The presence of breast microbiota has been known for several years. The etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. BRCA1/2 germline mutations and Li-Fraumeni syndrome are inherited as an autosomal dominant character but do not exhibit complete penetrance in carrier subjects. The local microbiota of the breast may influence breast tumor incidence and prognosis. Patients with genetically inherited impaired DNA repair may be more susceptible to bacterially induced DNA damage. This review aims to analyse the evidence that may allow an understanding of whether and how the penetrance of genetic predisposition may be influenced by breast microbiota. Graphical Abstract