Microbiome and Response to Therapy in Triple Negative Breast Cancer: A Systematic Review

Objectives: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is characterized by aggressive behavior, limited therapeutic options, and poor clinical outcomes. Due to the absence of hormone receptors and HER2 expression, systemic treatment relies predominantly on chemotherapy, which is associated with high rates of early recurrence and mortality. Emerging evidence suggests that alterations in the microbiome can contribute to TNBC progression and influence therapeutic response, particularly affecting the efficacy of chemotherapy and immunotherapy through immune-mediated mechanisms; however, its role in TNBC remains incompletely understood. This systematic review aims to explore the role of the microbiome in TNBC. It specifically aims to understand if the microbiome influences complete pathological response in TNBC. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed in PubMed and Cochrane databases. Fourteen eligible studies were included, encompassing preclinical and clinical evidence. Results: The findings indicate that both gut and tumor-associated microbiota significantly influence therapeutic response in TNBC, especially in the context of neoadjuvant chemotherapy (NACT) and immune checkpoint blockade (ICB). Higher microbial diversity and the presence of specific commensal taxa were consistently associated with enhanced antitumor immune activation, increased immune cell infiltration, and improved treatment efficacy. Conversely, antibiotic-induced dysbiosis was linked to reduced pCR rates and poorer clinical outcomes. Microbiome-modulating interventions demonstrated potential in restoring eubiosis and enhancing therapeutic responsiveness. Conclusions: Overall, the available evidence supports the microbiome as a promising biomarker and therapeutic target for optimizing treatment strategies and improving outcomes in TNBC.