Abstract

Simple SummaryThe tumor microenvironment (TME) in breast cancer plays important roles in tumor behavior and treatment response, making its pathologic assessment critical for disease management. Analysis of the TME is not only limited to research-based technologies but is now incorporated into routine histopathologic reporting for practical clinical application. This review covers the current understanding of the TME of breast cancer, its pathologic assessment relevant for prognostication and treatment strategies, and the cancer therapies that interacts with and/or exploits the TME in breast cancer. As actionable targets are constantly being discovered in the TME, the future approach to breast cancer therapy is likely to combine cancer cell elimination and TME modulation.The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.

Highlights

  • The understanding of the tumor microenvironment (TME) in breast cancer is rapidly evolving

  • Traditional grading and typing of breast cancer are based solely on the assessment of tumor cells, but pathologic assessment of the TME is incorporated in routine breast cancer management

  • Assessment of tumor-infiltrating lymphocytes (TILs) is recommended to be performed on H&E-stained tissue sections under light microscopy with high-power magnification and reported as percentage area occupied by mononuclear inflammatory cells, including lymphocytes and plasma cells, in the total stromal area within the tumor border (Figure 2) [3]

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Summary

Introduction

The understanding of the tumor microenvironment (TME) in breast cancer is rapidly evolving. Experimental findings in the TME are translated to clinical prognostic and therapeutic applications. Traditional grading and typing of breast cancer are based solely on the assessment of tumor cells, but pathologic assessment of the TME is incorporated in routine breast cancer management. This review covers the components of the TME and their interactions; how the TME reacts to and modulates conventional treatment modalities including radiotherapy and traditional chemotherapy; the laboratory assessment of TME; and the therapeutic agents mediating through changes of TME

Components of the TME and Their Interactions
The Local Microenvironment
The Regional Microenvironment
The Metastatic Microenvironment
The Tumor Microenvironment and Radiotherapy
The Tumor Microenvironment and Chemotherapy
Pathologic Assessment of the Tumor Microenvironment
Histologic Assessment of the Tumor Microenvironment
Concomitant Histologic Changes in Non-Tumorous Tissue
Dendritic Cell Markers
Other Markers
Molecular Methods
Findings
Conclusions
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