The Chemokine CCL5 as a Potential Prognostic Factor Predicting Disease Progression in Stage II Breast Cancer Patients

Abstract

Purpose: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers. Experimental Design: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed. Results: Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5+), the absence of ER-α (ER-α−), and the lack of PR expression (PR−) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-α−, improved by combining them together (CCL5+/ER-α−: P = 0.0001), being highly evident in the stage IIA subgroup [CCL5+/ER-α− (P = 0.0003); ER-α− (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5−/ER-α+ and CCL5−/PR+ were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-α and CCL5 were independent predictors of disease progression. Conclusions: CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5+/ER-α− combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

“…Conversely, the combinations of CCL5-negative/ER-a-positive and CCL5-negative/PR-positive in the stage II group as a whole were strongly correlative with an improved prognosis. 33 Furthermore, concomitant expression of the CCL5 and MCP-1 was observed in advanced human BC, 34 suggesting tumor-promoting interactions between these two chemokines. By immunohistochemistry analysis for the expression of CCL2, CCL5, IL-1b and TNF-a, Soria et al examined four groups of patients diagnosed with (i) benign breast disorders; (ii) ductal carcinoma in situ; (iii) invasive ducal carcinoma (IDC) without relapse; and (iv) IDC with relapse, respectively.…”

A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by regulating generation of myeloid-derived suppressor cells

“…In addition to changes in myeloid cells, there were higher frequencies in the more mature population of blasts and progenitors in KO mice. Previous studies by others have mostly focused on tumor-derived CCL5, and found overexpression of CCL5 in advanced stages of breast cancer [5]. In more recent years, mesenchymal stem cell-derived CCL5 has been shown to contribute to cancer cell motility, invasion and metastasis [49,50].…”

“…Tumor-derived CCL5 is detected in many clinical specimens of breast and cervical cancers; greater plasma levels in patients with progressive and more advanced disease than those in remission [5][6][7], and it constitutes a prominent part of a poor prognosis signature of inflammatory breast cancer [8,9]. The concentration of CCL5 was significantly higher in the groups of patients with or without axillary lymph node metastasis [10].…”

Association of chemokine CCL5 and systemic malignancies

“…CCL5 has also been shown to be a significant predictor of progression in patients with stage II breast cancer (Hahoshen et al 2006). In another study, tumors that expressed higher levels of CCL5 were more likely to metastasize in comparison with tumors that did not express as much CCL5 (Stormes et al 2005).…”