Impact of neoadjuvant chemotherapy on local breast microbiota and macrophages in ER-positive breast cancer with links to treatment response
8 affiliations
- 1Department of Surgery, GROW - School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands
- 2Department of Pathology, GROW - School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands
- 3Department of Pathology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands
- 4Department of Medical Biosciences, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands
- 5Department of Medical Microbiology, Infectious Diseases, and Infection Prevention, Maastricht University Medical Center+, Maastricht, The Netherlands
- 6NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
- 7Euregional Microbiome Center, Maastricht, The Netherlands
- 8Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
Abstract
Gut microbiota can modulate the tumor microenvironment and influence therapeutic outcomes in breast cancer. We hypothesized that similar interactions occur between the breast microbiota and tumor microenvironment. This exploratory study evaluated whether in situ microbial and macrophage densities differ between good and poor neoadjuvant chemotherapy responders and compared microbial density and composition post treatment with surgery-only controls. In 20 postmenopausal estrogen receptor-positive breast cancer patients, bacterial density was quantified by fluorescence in situ hybridization and macrophages density by multiplexed immunofluorescence in pre and post treatment tissue. Bacterial composition was analyzed by 16S rRNA sequencing of post-treatment resection specimens. Nine surgery-only patients served as controls. Neoadjuvant chemotherapy significantly reduced CD68 macrophage density, but not CD163 macrophages or bacterial density. Macrophages and bacterial densities were not correlated, and bacterial densities did not differ between good and poor responders. Higher pretreatment CD68 and CD163 macrophage densities predicted good response. Post treatment resections showed reduced bacterial density and alpha-diversity compared to surgery-only controls. These findings suggest that neoadjuvant chemotherapy affects local breast microbiota and macrophages, with macrophages as promising biomarkers to predict treatment response. The interaction between breast microbiota and local immunity deserves more attention in future research.
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BibTeX
@article{dieleman2026impact,
title = {{Impact of neoadjuvant chemotherapy on local breast microbiota and macrophages in ER-positive breast cancer with links to treatment response}},
author = {Sabine Dieleman and Carlijn Bruggeling and Phuc Dat Le and Lars E. Hillege and Catarina Correia Tavares Bernardino and Janine Ziemons and Renske Cremers and Arnaud Jacquerie and Alem Gusinac and Thomas H. A. Ederveen and Kiek Verrijp and John Penders and Anne-Marie Vos and Loes F. S. Kooreman and Heike I. Grabsch and Marjolein L. Smidt and Annemarie Boleij},
journal = {NPJ Breast Cancer},
year = {2026},
month = jul,
doi = {10.1038/s41523-026-01004-0},
url = {https://doi.org/10.1038/s41523-026-01004-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of neoadjuvant chemotherapy on local breast microbiota and macrophages in ER-positive breast cancer with links to treatment response
AU - Sabine Dieleman
AU - Carlijn Bruggeling
AU - Phuc Dat Le
AU - Lars E. Hillege
AU - Catarina Correia Tavares Bernardino
AU - Janine Ziemons
AU - Renske Cremers
AU - Arnaud Jacquerie
AU - Alem Gusinac
AU - Thomas H. A. Ederveen
AU - Kiek Verrijp
AU - John Penders
AU - Anne-Marie Vos
AU - Loes F. S. Kooreman
AU - Heike I. Grabsch
AU - Marjolein L. Smidt
AU - Annemarie Boleij
PY - 2026
DA - 2026/07/06
JO - NPJ Breast Cancer
DO - 10.1038/s41523-026-01004-0
UR - https://doi.org/10.1038/s41523-026-01004-0
AB - Gut microbiota can modulate the tumor microenvironment and influence therapeutic outcomes in breast cancer. We hypothesized that similar interactions occur between the breast microbiota and tumor microenvironment. This exploratory study evaluated whether in situ microbial and macrophage densities differ between good and poor neoadjuvant chemotherapy responders and compared microbial density and composition post treatment with surgery-only controls. In 20 postmenopausal estrogen receptor-positive breast cancer patients, bacterial density was quantified by fluorescence in situ hybridization and macrophages density by multiplexed immunofluorescence in pre and post treatment tissue. Bacterial composition was analyzed by 16S rRNA sequencing of post-treatment resection specimens. Nine surgery-only patients served as controls. Neoadjuvant chemotherapy significantly reduced CD68 macrophage density, but not CD163 macrophages or bacterial density. Macrophages and bacterial densities were not correlated, and bacterial densities did not differ between good and poor responders. Higher pretreatment CD68 and CD163 macrophage densities predicted good response. Post treatment resections showed reduced bacterial density and alpha-diversity compared to surgery-only controls. These findings suggest that neoadjuvant chemotherapy affects local breast microbiota and macrophages, with macrophages as promising biomarkers to predict treatment response. The interaction between breast microbiota and local immunity deserves more attention in future research.
SN - 2374-4677
ER -