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Immune checkpoint inhibitors (ICIs) have recently been incorporated into the treatment regimen for early-stage triple-negative breast cancer (TNBC) patients, improving surgical responses and decreasing the risk of relapse compared to chemotherapy alone. However, approximately 15% of patients will relapse within 5 years. The phase 1b/II PEARL trial investigated the effect of adding radiation therapy (RT) to ICI and chemotherapy in early TNBC and demonstrated further improvements in response.

Recent evidence demonstrates that the gut microbiome is associated with improved ICI responses in various cancers, with specific bacteria such as A. municiphila linked to improved progression-free survival and overall survival. In addition, certain gut bacteria have been associated with improved anticancer immune responses in the tumor, suggesting a mechanistic link between the gut microbiome and the tumor microenvironment.

However, there is limited research on the impact of the gut microbiome in breast cancer patients treated with ICIs. Using stool samples from the PEARL trial, we aim to evaluate whether the gut microbiome can predict responses following an ICI combination in early TNBC. In addition, we will investigate the biological mechanisms through which the gut microbiome affects anti-tumor immune responses by comparing gut profiles with immune markers in tumor biopsies. To our knowledge, this study will be the largest to date to investigate the gut microbiome in early TNBC, and the first to uncover the mechanistic role of the gut microbiome on anti-tumor immune responses in breast cancer.