Peripheral Blood Monocyte Abundance Predicts Outcomes in Patients with Breast Cancer

Author:

Axelrod Margaret L.1ORCID,Wang Yu2ORCID,Xu Yaomin2ORCID,Sun Xiaopeng1,Bejan Cosmin A.3ORCID,Gonzalez-Ericsson Paula I.4ORCID,Nunnery Sara1ORCID,Bergman Riley E.1ORCID,Donaldson Joshua1,Guerrero-Zotano Angel L.5ORCID,Massa Chiara6,Seliger Barbara6,Sanders Melinda47ORCID,Mayer Ingrid A.14,Balko Justin M.147ORCID

Affiliation:

1. 1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

2. 2Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

3. 3Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.

4. 4Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, Tennessee.

5. 5Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain.

6. 6Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

7. 7Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Abstract

Biomarkers of response are needed in breast cancer to stratify patients to appropriate therapies and avoid unnecessary toxicity. We used peripheral blood gene expression and cell-type abundance to identify biomarkers of response and recurrence in neoadjuvant chemotherapy–treated patients with breast cancer. We identified a signature of IFN and complement response that was higher in the blood of patients with pathologic complete response. This signature was preferentially expressed by monocytes in single-cell RNA sequencing. Monocytes are routinely measured clinically, enabling examination of clinically measured monocytes in multiple independent cohorts. We found that peripheral monocytes were higher in patients with good outcomes in four cohorts of patients with breast cancer. Blood gene expression and cell type abundance biomarkers may be useful for prognostication in breast cancer. Significance: Biomarkers are needed in breast cancer to identify patients at risk for recurrence. Blood is an attractive site for biomarker identification due to the relative ease of longitudinal sampling. Our study suggests that blood-based gene expression and cell-type abundance biomarkers may have clinical utility in breast cancer.

Funder

Susan G. Komen

HHS | NIH | National Cancer Institute

U.S. Department of Defense

Vanderbilt-Ingram Cancer Center

HHS | National Institutes of Health

Dr. Mildred Scheel Stiftung für Krebsforschung

Deutsche Krebshilfe

Publisher

American Association for Cancer Research (AACR)

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4. Differential expression analysis for sequence count data;Anders;Genome Biol,2010

5. Heavy-Tailed prior distributions for sequence count data: removing the noise and preserving large differences;Zhu;Bioinformatics,2019

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