Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment

SIMPLE SUMMARY: In this review we discuss the recent knowledge about the role of breast and gut microbiome in the pathogenesis of breast cancer. We examine the proposed mechanisms of interaction between breast tumors and the microbiome. We focus on the role of the microbiome in: (i) the development and maintenance of estrogen metabolism through bacterial beta-glucuronidase enzymes (ii) the regulation of the host´s immune system and tumor immunity by Treg lymphocyte proliferation through bacterial metabolites such as butyrate and propionate (SCFAs), (iii) the induction of chronic inflammation, (iv) the response and/or resistance to treatments and (v) the epigenetic reprogramming. Moreover, we also discuss that diet, probiotics and prebiotics could exert important anticarcinogenic effects in breast cancer that could indicate their employment as adjuvants in standard-of-care breast cancer treatments. Overall, these findings could give new insights for building up novel strategies for breast cancer prevention and treatment. ABSTRACT: In breast cancer (BC) the employment of sequencing technologies for metagenomic analyses has allowed not only the description of the overall metagenomic landscape but also the specific microbial changes and their functional implications. Most of the available data suggest that BC is related to bacterial dysbiosis in both the gut microenvironment and breast tissue. It is hypothesized that changes in the composition and functions of several breast and gut bacterial taxa may contribute to BC development and progression through several pathways. One of the most prominent roles of gut microbiota is the regulation of steroid-hormone metabolism, such as estrogens, a component playing an important role as risk factor in BC development, especially in postmenopausal women. On the other hand, breast and gut resident microbiota are the link in the reciprocal interactions between cancer cells and their local environment, since microbiota are capable of modulating mucosal and systemic immune responses. Several in vivo and in vitro studies show remarkable evidence that diet, probiotics and prebiotics could exert important anticarcinogenic effects in BC. Moreover, gut microbiota have an important role in the metabolism of chemotherapeutic drugs and in the activity of immunogenic chemotherapies since they are a potential dominant mediator in the response to cancer therapy. Then, the microbiome impact in BC is multi-factorial, and the gut and breast tissue bacteria population could be important in regulating the local immune system, in tumor formation and progression and in therapy response and/or resistance.