AUTHOR=Wang Changjun , Lin Yan , Zhu Hanjiang , Zhou Yidong , Mao Feng , Huang Xin , Sun Qiang , Li Chenggang 

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.905846

DOI=10.3389/fonc.2022.905846

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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, <italic>P</italic>&lt;0.001) and shorter DFS (HR 1.77, 95% CI, 1.08–2.89, <italic>P</italic>=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 <italic>P</italic>&lt;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 <italic>P</italic>&lt;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 <italic>P</italic>&lt;0.05).</p></sec><sec><title>Conclusion</title><p>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 <italic>in vivo</italic> experiments are needed to elucidate the underlying mechanism of TAMs.</p></sec><sec><title>Systematic Review Registration</title><p><uri xlink:href="https://www.crd.york.ac.uk" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.crd.york.ac.uk</uri>/prospero/display_record.php?ID=CRD42022304853, identifier CRD42022304853.</p></sec>