The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

Abstract

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4 þ and CD8 þ ) and macrophage (CD68 þ ) infiltration, proliferative (Ki-67) index and microvessel density (CD34 þ ) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (Po0.05) and macrophage (Po0.05) infiltration and microvessel density (Po0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (Po0.01), negative hormonal receptor (Po0.10), lower albumin concentrations (Po0.01), increased tumour proliferation (Po0.05), increased tumour microvessel density (Po0.05), the extent of locoregional control (Po0.0001) and limited systemic treatment (Pp0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35 -16.85, P ¼ 0.015), locoregional treatment (HR 3.64, 95% CI 1.04 -12.72, P ¼ 0.043) and systemic treatment (HR 2.29, 95% CI 1.23 -4.27, P ¼ 0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (Po0.05) was independently associated with poorer cancerspecific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer.

Expression of Vascular Notch Ligand Delta-Like 4 and Inflammatory Markers in Breast Cancer

“…The data suggest that macrophages predominate in inflammatory infiltrates, with significant implications for angiogenesis in breast cancer, which has been attributed, in part, to the secretion of proangiogenic factors by macrophages. 56 Consistent with previously published observations, expression of the myeloid cell marker CD68 57 was a weak adverse prognostic factor in univariate analyses of overall survival, but not relapsefree survival. Expression of DC-SIGN, an immature myeloid dendritic cell marker, was also a significant prognostic factor in univariate analyses of overall survival, but not relapse-free survival.…”

Loss of p120-Catenin Induces Metastatic Progression of Breast Cancer by Inducing Anoikis Resistance and Augmenting Growth Factor Receptor Signaling

“…In line with this, we found that loss of p120 results in the development of stromal dense and macrophage-rich mammary tumors. Furthermore, we show that loss of p120 leads to secretion of several cytokines, which may control the recruitment of inflammatory cells (e.g., macrophages) that have been implicated in inflammation-associated cancer initiation and promotion (48) and are correlated with poor prognosis in breast cancer (49,50). Moreover, it has been well established that mammary tumor cells may instigate a paracrine loop that involves the production of chemoattractants and subsequent recruitment of EGF-producing macrophages, resulting in activation of prometastatic pathways in tumor cells (51,52).…”

Expression of cluster of differentiation 34 and vascular endothelial growth factor in breast cancer, and their prognostic significance

“…In addition, the clinical stage of breast cancer was determined to be a major contributor to a poor prognosis. Similarly, Murri et al (15) reported the expression of CD34 in 168 patients with early invasive breast cancer. This study identified that an increased tumor MVD was correlated with the OS of the patients (P<0.05), and multivariate analysis identified albumin concentration, topical therapy, systemic therapy and tumor MVD as independent factors for predicting a poor prognosis (P<0.05).…”