Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Nov 27

PMID 34830923

Citations 13

Authors

Nazia Riaz

Samantha Burugu

Angela S Cheng

Samuel C Y Leung

Dongxia Gao

Torsten O Nielsen

Affiliations

Soon will be listed here.

Abstract

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of mRNA with immune infiltrates and prognosis. Following a prespecified training-validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.

Citing Articles

Insights into CSF-1R Expression in the Tumor Microenvironment.

Tomassetti C, Insinga G, Gimigliano F, Morrione A, Giordano A, Giurisato E Biomedicines. 2024; 12(10).

PMID: 39457693 PMC: 11504891. DOI: 10.3390/biomedicines12102381.

Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer.

Padzinska-Pruszynska I, Kucharzewska P, Matejuk A, Gorczak M, Kubiak M, Taciak B Int J Mol Sci. 2024; 25(19).

PMID: 39409110 PMC: 11476577. DOI: 10.3390/ijms251910781.

The carcinogenic capacity of arsenic in normal epithelial breast cells and double-positive breast cancer cells.

Zimta A, Cenariu D, Tigu A, Moldovan C, Jurj A, Pop L Med Pharm Rep. 2024; 97(2):184-195.

PMID: 38746032 PMC: 11090272. DOI: 10.15386/mpr-2682.

CSF-1R in Cancer: More than a Myeloid Cell Receptor.

Cersosimo F, Lonardi S, Ulivieri C, Martini P, Morrione A, Vermi W Cancers (Basel). 2024; 16(2).

PMID: 38254773 PMC: 10814415. DOI: 10.3390/cancers16020282.

Challenges and prospects of CSF1R targeting for advanced malignancies.

Moeller A, Kurzrock R, Botta G, Adashek J, Patel H, Lee S Am J Cancer Res. 2023; 13(7):3257-3265.

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