Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature
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Xixi Zhao1,*, Jingkun Qu2,*, Yuchen Sun3, Jizhao Wang2, Xu Liu2, Feidi Wang1, Hong Zhang1, Wen Wang1, Xingcong Ma1, Xiaoyan Gao1 and Shuqun Zhang1
1 Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China
2 The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China
3 The Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, P.R. China
* These authors have contributed equally to this work
Shuqun Zhang, email:
Keywords: breast cancer, tumor associated macrophages, prognosis, meta-analysis
Received: September 12, 2016 Accepted: February 06, 2017 Published: February 25, 2017
Purpose: Tumor associated macrophages (TAMs) are important prognostic factors and have been proved to be associated with the invasion and migration of various cancer. However, the relationship between TAMs and breast cancer outcomes remains unclear.
Experimental Design: Sixteen studies with a total of 4,541 breast cancer patients were included in this meta-analysis. Correlation of TAMs with overall survival (OS), disease-free survival(DFS), relapse-free survival (RFS), breast cancer special survival (BCSS) and clinicopathological features were analyzed. Survival data and clinicopathological value were integrated by analyzing hazard ratio(HR) and odds ratio(OR) separately and using Fixed-effect or Random-effect model according to heterogeneity. All statistical tests were two-sided.
Results: OS and DFS were correlated with high density of TAMs with HR= 1.504(1.200, 1.884)/ 2.228(1.716, 2.892) respectively. And subgroup analysis of location and biomarker in OS and DFS group showed prognosis was associated with TAMs distribution and biomarker selection. Besides, TAMs high infiltration was significantly related to age, size, histologic grade, ER/PR status, basal phenotype and vascular invasion.
Conclusion: High density of TAMs was associated with poor survival rates of breast cancer. TAMs in stroma are associated with worse outcome than that in nest and using CD68 as a biomarker for TAMs to evaluate the risk is better than CD163 or CD206 alone. Moreover, high infiltration of TAMs was significantly associated with negative hormone receptor status and malignant phenotype. TAMs infiltration can serve as a novel prognostic factor in breast cancer patients.
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