Understanding and harnessing triple-negative breast cancer-related microbiota in oncology

Abstract

Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects.

Exploring the human microbiome – A step forward for precision medicine in breast cancer

“…The microbial profiles found in adjacent normal tissue were more similar to the tumor microbiome than those found in nonmatched healthy tissue controls, suggesting that the TME resident tumor microbiota can extend to surrounding tissues, implying an active role in tumorigenesis. 13,43,51 Recent evidence also supports the idea that intra-tumoral bacteria can localize within the tumor and immune cells in various cancer types, including TNBC. Intriguingly, recent studies suggest that the influence of gut microbiome on tumor-infiltrating lymphocytes (TILs) profile is associated with better treatment outcomes in TNBCs and other cancers.…”

“…Other studies have shown that TNBC has the least taxonomic diversity among all breast cancer types and a higher abundance of biofilm‐forming bacterial strains, such as Aggregatibacter and Caulobacter . The microbial profiles found in adjacent normal tissue were more similar to the tumor microbiome than those found in non‐matched healthy tissue controls, suggesting that the TME resident tumor microbiota can extend to surrounding tissues, implying an active role in tumorigenesis 13,43,51 . Recent evidence also supports the idea that intra‐tumoral bacteria can localize within the tumor and immune cells in various cancer types, including TNBC.…”

“…Dysbiosis, characterized by an imbalance in the microbial community, has been associated with various diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer 10 . Studies suggest that microbial dysbiosis can contribute to carcinogenesis through mechanisms such as metabolite production, inflammation, immune dysregulation, DNA damage, and altered drug metabolism 11–17 . Human microbiome research has emerged as a promising field with transformative potential in the diagnosis, monitoring, treatment, and management of various diseases, including cancer.…”

“…10 Studies suggest that microbial dysbiosis can contribute to carcinogenesis through mechanisms such as metabolite production, inflammation, immune dysregulation, DNA damage, and altered drug metabolism. 11 , 12 , 13 , 14 , 15 , 16 , 17 Human microbiome research has emerged as a promising field with transformative potential in the diagnosis, monitoring, treatment, and management of various diseases, including cancer. The WHO's World Cancer Report–2020 highlights the role of the human microbiota in cancer development and therapy.…”

A Holistic Approach to Hard-to-Treat Cancers: The Future of Immunotherapy for Glioblastoma, Triple Negative Breast Cancer, and Advanced Prostate Cancer

“…In TNBC, however, the negative impact of microbiota-mediated oestrogen abundance does not seem to occur, likely due to the lack of ERa expression. TNBCs have alternative oestrogen signalling pathways which render them responsive to circulating hormones [ 124 ]. Interestingly, studies suggest that receptors such as ERb, G protein-coupled oestrogen receptor 1, and oestrogen-related receptors have anti-cancer effects and that, when these are expressed in TNBCs, prognosis seems to be better [ 125 ].…”