Abstract

The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative biopsies to increase tumor supportive elements in the microenvironment, whereas, in humans, the impact of CNB on the host’s immunologic response has not been investigated. In this pilot study, we compared the expression of CCL2/CCR2 pathway components at the protein level in samples from CNBs to those from the corresponding resected tumors from 52 patients with primary breast cancer. We found an increased expression of CD163, CD14 and CCR2 in monocytes/macrophages and a slight decrease of CCL2 in the malignant epithelium in the tumors after the biopsy. The increased infiltration of immunosuppressive monocytes/macrophages and the decreased tumor cell CCL2 expression, presumably due to the CCR2 availability-dependent CCL2 internalization, suggest that CNB enhances the activity of the CCL2/CCR2 pathway, and this finding warrants confirmatory examination. The switch in the context-dependent role of CCL2 on the polarization of macrophages may lead to increased tumor supportive function both locally and in the peripheral immune machinery. The future directions in breast cancer should include early interventions to support the tumor surveillance of the host.

Highlights

  • CD14 expressed in monocytes/macrophages the tumor cells CCR2, in one pair of aand and were the corresponding excised tumor

  • We focused on the activity of the CCL2/CCR2 pathway and on the infiltration of CCR2, CD163 and CD14-positive monocytes/macrophages, known to be recruited via the CCL2 gradient

  • We found a fraction of stromal lymphocytes expressing CCL2, which is in accordance with previous reports of CCL2 being produced by tumor cells themselves and by stromal cells in response to various inflammatory stimuli [21,22,23,24]

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Summary

Introduction

Patients with clinically and/or radiologically malignant lesions in breast tissue undergo core needle biopsy (CNB) to verify the diagnosis of invasive cancer. CNB has a high overall accuracy [1], and it is currently established as a critical part in the process of diagnosing breast tissue lesions. Malignant tumors are removed as soon as the pathologic report of the needle sample confirms the diagnosis, and investigations on the spread of the disease have been performed, typically with a delay of two to four weeks. The impact of CNB on the biology of the tumor is largely unknown. In an early study in breast cancer comparing excision surgery only to excision preceded by needle biopsy, no difference in

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