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.