# Gut microbiota diversity is prognostic in metastatic hormone receptor‐positive breast cancer patients receiving chemotherapy and immunotherapy

## TL;DR

The gut microbiota's diversity predicts survival in hormone receptor-positive breast cancer patients undergoing chemotherapy and immunotherapy.

## Contribution

This study identifies gut microbiota alpha diversity as a potential prognostic biomarker in HR+ metastatic breast cancer.

## Key findings

- High baseline alpha diversity correlates with prolonged progression-free and overall survival.
- Alpha diversity remains significant even after adjusting for prior chemotherapy and other factors.
- High-grade immune-related toxicity is associated with high alpha diversity.

## Abstract

Immune checkpoint blockade (ICB) is standard treatment in several cancer types, despite not being proven efficacious in metastatic hormone receptor‐positive breast cancer (HR+ mBC). The gut microbiota is associated with patient outcome and toxicity from cancer therapy, although limited data are available for breast cancer. In the randomized phase 2b trial ICON, immunomodulating chemotherapy was investigated in combination with dual ICB in HR+ mBC. To determine whether gut microbiota could inform prognosis, we performed 16S (V3‐V4) rRNA sequencing on fecal samples collected at baseline and after 8 weeks of study treatment. We showed that high alpha diversity before treatment was associated with prolonged progression‐free survival (PFS; primary trial endpoint) and overall survival. Alpha diversity was lower in patients with prior chemotherapy in the metastatic setting. However, alpha diversity remained significantly associated with PFS after correcting for prior chemotherapy and other factors in bivariate analyses. High‐grade immune‐related toxicity was also associated with high alpha diversity. These findings suggest that high alpha diversity should be further investigated as a positive prognostic factor in HR+ mBC and approaches to increase alpha diversity could potentially improve clinical outcome.

In this exploratory study, we investigated the relationship between the gut microbiota and outcome in patients with metastatic hormone receptor‐positive breast cancer, treated in a randomized clinical trial with chemotherapy alone or chemotherapy in combination with immune checkpoint blockade. Our data suggest a prognostic role of alpha diversity in this population.