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REVIEW

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

Mariana Lopes1,#, Carlos Vila Nova2,3,#, Rui Caetano Oliveira3,4, Fernando Schmitt5, Fernando Mendes1,6,7,8,9,*, Diana Martins1,6,7,8
1 Escola Superior de Tecnologia da Saúde de Coimbra (ESTESC), Polytechnic University of Coimbra, Coimbra, Portugal
2 Surgery Unit, Unidade Local de Saúde do Baixo Mondego, Figueira da Foz, Portugal
3 Faculty of Medicine, University of Coimbra, Coimbra, Portugal
4 Centro de Anatomia Patológica Germano de Sousa, Coimbra, Portugal
5 RISE-Health, Department of Pathology, Medical Faculty of Porto University, Porto, Portugal
6 H&TRC—Health & Technology Research Center, Coimbra Health School, Polytechnic University of Coimbra, Coimbra, Portugal
7 Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Biophysics Institute of Faculty of Medicine, University of Coimbra, Coimbra, Portugal
8 Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
9 European Association of Biomedical Scientists, Brussels, Belgium
* Corresponding Author: Fernando Mendes. Email: email
# These authors contributed equally to this work as the first author
(This article belongs to the Special Issue: Advances in Targeted and Precision Medicine in Breast Oncology)

Oncology Research https://doi.org/10.32604/or.2026.074215

Received 06 October 2025; Accepted 05 February 2026; Published online 20 March 2026

Abstract

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.

Keywords

Triple negative breast neoplasms; microbiota; chemotherapy; pathological complete response; immunotherapy

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