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Mendelian Randomization Study: The Impact of Gut Microbiota on Survival in HR+ Breast Cancer Patients Under Different Treatment Regimens Through the Modulation of Immune Cell Phenotypes

Clin Breast Cancer. 2025 Aug 5:S1526-8209(25)00221-6. doi: 10.1016/j.clbc.2025.07.024. Online ahead of print.

ABSTRACT

BACKGROUND: Emerging evidence suggests that the gut microbiota (GM) may influence the progression of breast cancer by modulating immune responses. Given the vast diversity of GM and immune cell phenotypes, this study aimed to utilize the most advanced and comprehensive data to explore the causal relationships among the GM, immune cell phenotypes, and survival rates in hormone receptor-positive (HR+) breast cancer patients under different treatment regimens.

METHODS: We investigated the causal relationships between the GM, immune cell phenotypes, and survival rates in HR+ breast cancer patients treated with 11 distinct therapeutic strategies using Mendelian randomization. Inverse variance weighted analysis served as the primary statistical method. Additionally, we explored whether immune cell phenotypes act as mediators in the pathway from the GM to HR+ breast cancer survival rates.

RESULTS: In this comprehensive study, we identified 116 distinct GM species that established causal links with survival rates across 11 different subgroups of HR+ breast cancer patients. Furthermore, we discovered 13 potential pathways through which the GM might influence immune cell phenotypes, thereby affecting patient survival rates.

CONCLUSION: The GM is causally associated with survival rates in HR+ breast cancer patients treated with 11 different therapeutic strategies, and immune cell phenotypes serve as mediators in the pathway from the GM to HR+ breast cancer survival rates.

PMID:40915962 | DOI:10.1016/j.clbc.2025.07.024

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