Despite breast cancer being long thought to be "immunologically cold," within early, triple-negative breast cancer (TNBC), there has been exciting advances with the use of immune checkpoint modulation combined with neoadjuvant chemotherapy. We review the major trials that have investigated combination immunochemotherapy in the neoadjuvant setting, reviewing both the pathological complete response rates and the maturing data regarding event-free and overall survival. Strategies to deescalate adjuvant therapy in patients with preserving excellent clinical outcome, as well as exploration of combinatorial adjuvant therapies to improve outcome in those with extensive residual are the next-generation challenges. In addition to refinement of existing biomarkers, such as PD-L1, TILs, and tumor mutational burden (TMB), exploration of topics like the microbiome as both a biomarker and a therapeutic has shown promise in other cancer types, which motivates investigating these in breast cancer.

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.