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. 2022 Jun 30:12:905846.
doi: 10.3389/fonc.2022.905846. eCollection 2022.

The Prognostic and Clinical Value of Tumor-Associated Macrophages in Patients With Breast Cancer: A Systematic Review and Meta-Analysis

Changjun Wang  1 , Yan Lin  1 , Hanjiang Zhu  2 , Yidong Zhou  1 , Feng Mao  1 , Xin Huang  1 , Qiang Sun  1 , Chenggang Li  3   4
Affiliations

The Prognostic and Clinical Value of Tumor-Associated Macrophages in Patients With Breast Cancer: A Systematic Review and Meta-Analysis

Changjun Wang et al. Front Oncol. .

Abstract

Background: The prognostic and clinical value of tumor-associated macrophages (TAMs) in patients with breast cancer (BCa) remains unclear. We conducted the current meta-analysis to systematically evaluate the association of CD68+ and CD163+ TAM density with the prognosis and clinicopathologic features of BCa patients.

Methods: Searches of Web of Science, PubMed, and EMBASE databases were performed up to January 31, 2022. The meta-analysis was conducted using hazard risks (HRs) and 95% confidence intervals (CIs) for survival data including overall survival (OS), disease-free survival (DFS), and BCa specific survival. Sensitivity and meta-regression analyses were also conducted to identify the robustness of the pooled estimates.

Results: Our literature search identified relevant articles involving a total of 8,496 patients from 32 included studies. Our analysis indicates that a high CD68+ TAM density in the tumor stoma was significantly linked with poor OS (HR 2.46, 95% CI, 1.83-3.31, P<0.001) and shorter DFS (HR 1.77, 95% CI, 1.08-2.89, P=0.02) compared to low CD68+ TAM density. A significant association was also found in the tumor nest. Analysis of CD163+ TAM density showed similar results (all P<0.001). Notably, the pooled analysis with multivariate-adjusted HRs for OS and DFS also found that a high TAM density was significantly related to poorer outcomes for BCa patients (all P<0.05). In addition, BCa patients with high TAM density were more likely to have larger tumors, no vascular invasion, and positive estrogen receptor expression (all P<0.05).

Conclusion: This meta-analysis indicates that a high CD68+ and CD163+ TAM density is associated with poor OS and shorter DFS in BCa patients. Further clinical studies and in vivo experiments are needed to elucidate the underlying mechanism of TAMs.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304853, identifier CRD42022304853.

Keywords: breast cancer; meta-analysis; survival; systematic review; tumor-associated macrophages.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of article selection.
Figure 2
Figure 2
Forest plots of HRs for OS between high and low CD68+ TAM density in BCa patients. (A) HRs of OS in raw data for CD68+ TAMs in the TN of BCa; (B) HRs of OS in raw data for CD68+ TAMs in the TS of BCa; (C) HRs of OS with adjusted measures for CD68+ TAMs in the TN of BCa; (C) HRs of OS with adjusted measures for CD68+ TAMs in the TS of BCa.
Figure 3
Figure 3
Forest plots of HRs for DFS between high and low CD68+ TAM density in BCa patients. (A) HRs of DFS in raw data for CD68+ TAMs in the TN of BCa; (B) HRs of DFS in raw data for CD68+ TAMs in the TS of BCa; (C) HRs of DFS with adjusted measures for CD68+ TAMs in the TN of BCa; (D) HRs of DFS with adjusted measures for CD68+ TAMs in the TS of BCa.
Figure 4
Figure 4
Forest plots of HRs for OS between high and low CD163+ TAM density in BCa patients. (A) HRs of OS in raw data for CD163+ TAMs in the TN of BCa; (B) HRs of OS in raw data for CD163+ TAMs in the TS of BCa; (C) HRs of OS with adjusted measures for CD163+ TAMs in the TN of BCa; (D) HRs of OS with adjusted measures for CD163+ TAMs in the TS of BCa.
Figure 5
Figure 5
Forest plots of HRs for DFS between high and low CD163+ TAM density in BCa patients. (A) HRs of DFS in raw data for CD163+ TAMs in the TN of BCa; (B) HRs of DFS in raw data for CD163+ TAMs in the TS of BCa; (C) HRs of DFS with adjusted measures for CD163+ TAMs in the TN of BCa; (D) HRs of DFS with adjusted measures for CD163+ TAMs in the TS of BCa.
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