Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation

Abstract

Background Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to 1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, 2) characterize the type of inflammatory response present, and 3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. Methods The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e. immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. Results We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Conclusions Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings may carry relevance in the clinical management of breast cancer.

Potential impact of invasive surgical procedures on primary tumor growth and metastasis

“…Still, even small wounds to the tumor created by needle biopsy can rapidly promote pro-inflammatory factors such as S100A8, CXCL2, CCL3, and COX2 followed by a significant increase in the number of myeloid derived suppressor cells in the tumor [ 49 ]. Eosinophils that controversially have been reported as indicators of both favorable [ 52 , 53 ] and poor prognosis [ 54 , 55 ] have also been found to infiltrate the tumor after biopsy in breast cancer patients [ 56 ].…”

Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity

“…120, 121). Pancreatic ductal ligation (PDL), which serves as a model of pancreatic wounding, causes broad degeneration of acinar cells.…”

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

“…Mechanical interventions (core needle biopsies and surgery) can cause wound-induced inflammatory oncotaxis, which influences the natural history of breast cancer (129). Data from several studies show that biopsies and surgery can cause inflammatory oncotaxis thus increasing tissue angiogenesis and spread of tumor cells (134)(135)(136)(137)(138)(139)(140). Invasive and metastatic behavior would be expected for breast cancer cells with myeloid properties (123).…”