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Review
. 2023 Mar;11(1):27-48.
doi: 10.1007/s40487-022-00214-3. Epub 2022 Dec 9.

Breast Cancer Survival Outcomes and Tumor-Associated Macrophage Markers: A Systematic Review and Meta-Analysis

Eleanor Allison  1 , Senarath Edirimanne  1 , Jim Matthews  2 , Stephen J Fuller  3
Affiliations
Review

Breast Cancer Survival Outcomes and Tumor-Associated Macrophage Markers: A Systematic Review and Meta-Analysis

Eleanor Allison et al. Oncol Ther. 2023 Mar.

Abstract

Introduction: Tumor-associated macrophages (TAMs) in breast cancer are associated with a poor prognosis. Early studies of TAMs were largely limited to the pan-macrophage marker CD68, however, more recently, an increasing number of studies have used CD163, a marker expressed by alternatively activated M2 macrophages and TAM subsets. We hypothesized that CD163-positive (CD163+) TAMs would be a better predictor of survival outcomes in breast cancer compared to CD68+ TAMs.

Methods: We performed a systematic literature search of trials (from 1900 to August 2020) reporting overall survival (OS) or progression-free survival (PFS), breast cancer-specific survival (BCSS), TAM phenotype, and density. Thirty-two studies with 8446 patients were included. Meta-analyses were carried out on hazard ratios (HRs) for survival outcomes of breast cancer patients with a high density of TAMs (CD68+ and/or CD163+) compared to a low density of TAMs.

Results: A high density of TAMs (CD68+ and/or CD163+) was associated with decreased OS (HR 1.69, 95% CI 1.37-2.07) and reduced PFS (HR 1.64; 95% CI 1.35-1.99). Subgrouping by CD marker type showed a lower OS for high density of CD163+ TAMs (HR 2.24; 95% CI 1.71-2.92) compared to a high density of CD68+ TAMs (HR 1.5; 95% CI 1.12-2). A high density of TAMs (CD68+ and/or CD163+) in triple-negative breast cancer (TNBC) cases was associated with lower OS (HR 2.81, 95% CI 1.35-5.84).

Conclusion: Compared to CD68+ TAMs, a high density of CD163+ TAMs that express a similar phenotype to M2 macrophages are a better predictor of poor survival outcomes in breast cancer.

Keywords: Breast cancer; CD163; CD68; Prognosis; Triple-negative breast cancer; Tumor-associated macrophage.

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Figures

Fig. 1
Fig. 1
Process of study selection for the meta-analysis
Fig. 2
Fig. 2
Forest plots of HRs for TAM density and outcomes. Forest plots and meta-analyses of studies evaluating HRs of high density of TAMs compared to low density. A OS, B PFS, C BCSS. Note: Where reported, CD marker and tumor location were analyzed separately
Fig. 2
Fig. 2
Forest plots of HRs for TAM density and outcomes. Forest plots and meta-analyses of studies evaluating HRs of high density of TAMs compared to low density. A OS, B PFS, C BCSS. Note: Where reported, CD marker and tumor location were analyzed separately
Fig. 3
Fig. 3
Forest plots of HRs for high density of CD68+  TAMs compared to high density of CD163+ TAMs. A OS, B PFS
Fig. 4
Fig. 4
Forest plots of HRs for high density of TAMs in TNBC. A OS, B PFS
Fig. 5
Fig. 5
Forest plots of HRs for high density of TAMs and tumor location. A OS, B PFS
Fig. 6
Fig. 6
Funnel graphs for assessment of potential publication bias in studies of density of TAMs in patients with breast cancer. A OS, B PFS, C BCSS
See this image and copyright information in PMC

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