Abstract

Simple SummaryChronic inflammation is an important cause of multiple cancers. While chronic inflammation is present in breast cancer and may influence its outcome, its role in the initiation and development of breast cancer is unclear. A review of the literature was conducted to determine if chronic inflammatory processes are present, both systemically and in normal breast tissue, which may contribute to the development of breast cancer in women. This indicates that several chronic inflammatory factors may influence breast cancer development, with some such as adipose tissue and obesity occurring early in breast carcinogenesis, while others, such as the microbiome and inflammation from genomic changes, may occur with the transition to malignancy. Chronic inflammation appears to be an important risk factor for breast cancer and may influence both the development and conduct of breast cancer.Chronic inflammation contributes to the malignant transformation of several malignancies and is an important component of breast cancer. The role of chronic inflammation in the initiation and development of breast cancer from normal breast tissue, however, is unclear and needs to be clarified. A review of the literature was conducted to define the chronic inflammatory processes in normal breast tissue at risk for breast cancer and in breast cancer, including the role of lymphocyte and macrophage infiltrates, chronic active adipocytes and fibroblasts, and processes that may promote chronic inflammation including the microbiome and factors related to genomic abnormalities and cellular injury. The findings indicate that in healthy normal breast tissue there is systemic evidence to suggest inflammatory changes are present and associated with breast cancer risk, and adipocytes and crown-like structures in normal breast tissue may be associated with chronic inflammatory changes. The microbiome, genomic abnormalities, and cellular changes are present in healthy normal breast tissue, with the potential to elicit inflammatory changes, while infiltrating lymphocytes are uncommon in these tissues. Chronic inflammatory changes occur prominently in breast cancer tissues, with important contributions from tumor-infiltrating lymphocytes and tumor-associated macrophages, cancer-associated adipocytes and crown-like structures, and cancer-associated fibroblasts, while the microbiome and DNA damage may serve to promote inflammatory events. Together, these findings suggest that chronic inflammation may play a role in influencing the initiation, development and conduct of breast cancer, although several chronic inflammatory processes in breast tissue may occur later in breast carcinogenesis.

Highlights

  • Chronic inflammation has been recognized to play an important role in cancer since1863 when Rudolph Virchow noted leucocytes in neoplastic tissues and suggested that the “lymphoreticular infiltrate” reflected the origin of cancer at sites of chronic inflammation [1]

  • Normal breast tissue from healthy women contains multiple immune cells, including CD4+ and CD8+ T lymphocytes, macrophages and dendritic cells, which could potentially mediate chronic inflammatory changes [8]. These findings suggest chronic inflammatory changes may be associated with normal breast tissue and influence the risk for breast cancer

  • Chronic inflammation is present in breast cancer and may be associated with multiple cellular changes including tumor infiltrating lymphocytes, tumor associated macrophages, crown-like structures of adipocytes, cancer-associated fibroblasts, and the tumor cells themselves

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Summary

Introduction

Chronic inflammation has been recognized to play an important role in cancer since. 1863 when Rudolph Virchow noted leucocytes in neoplastic tissues and suggested that the “lymphoreticular infiltrate” reflected the origin of cancer at sites of chronic inflammation [1]. Normal breast tissue from healthy women contains multiple immune cells, including CD4+ and CD8+ T lymphocytes, macrophages and dendritic cells, which could potentially mediate chronic inflammatory changes [8] Together, these findings suggest chronic inflammatory changes may be associated with normal breast tissue and influence the risk for breast cancer. Chronic inflammation is present in breast cancer and may be associated with multiple cellular changes including tumor infiltrating lymphocytes, tumor associated macrophages, crown-like structures of adipocytes, cancer-associated fibroblasts, and the tumor cells themselves These chronic inflammatory actions may be triggered by products from microorganisms such as pathogen-associated molecular patterns (PAMPS) in the breast cancer, or cellular products released from injured or necrotic cells, such as damage-associated molecular patterns (DAMPS) and mediated by cytokines and chemokines secreted from associated innate or adaptive immune cells.

Materials and Methods
Chronic Inflammatory Changes Associated with Normal Breast Tissue
Evidence of Inflammation Associated with Breast Cancer Risk
Immune Cells and Inflammatory Cell Infiltrates in Normal Breast Tissue
Fibroblasts in Normal Breast Tissue
Potential Contributors to Chronic Inflammation in Normal Breast Tissue
Chronic Inflammatory Cell Infiltrates in Breast Cancer Tissues
Potential Contributors to Chronic Inflammation in Breast Cancer
Cancer-Associated Adipocytes and Crown-Like Structures
Chronic Inflammation and the Promotion of Metastatic Disease
Findings
Summary and Conclusions
Full Text
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