The chemokine receptor CXCR4 as a novel independent prognostic marker for node‐positive breast cancer patients

Background Node‐positive breast cancer patients are a high‐risk group. However, not all such patients will succumb to the disease. The molecular basis for this biologic heterogeneity is poorly understood. The chemokine receptor CXCR4 is a marker of metastatic disease. Its prognostic role in node‐positive patients is unknown. We postulate that high CXCR4 overexpression in node‐positive breast cancer specimens predicts a poor outcome. Methods 185 node‐positive breast cancer patients were evaluated. All had standardized treatment and surveillance protocols. CXCR4 levels were detected with Western blots. Results were quantified against 1 µg of HeLa cells. CXCR4 expression was defined as high (≥7.5‐fold) or low (<7.5‐fold). Primary endpoints were cancer recurrence and death. Statistical analyses were Kaplan–Meier curves, log‐rank test, and Cox proportional hazard model, with a P ‐value of ≤0.05 as significant. Results The mean follow‐up time was 54 months; 148 patients (80%) had low CXCR4 and 37 patients (20%) had high CXCR4 level. The 5‐year overall survival (OS) for the low and high CXCR4 group was 69% and 57%, respectively ( P  = 0.02). The 5‐year disease‐free survival (DFS) for the low and high CXCR4 group was 62% and 53%, respectively ( P  = 0.08). On multivariate analysis, T stage ( P  = 0.001) and grade ( P  = 0.04) were independent predictors of DFS, while T stage ( P  = 0.005), grade ( P  = 0.024), and CXCR4 level ( P  = 0.01) were independent predictors of OS. Conclusion High CXCR4 level in cancer specimens independently predicts a poor outcome for patients with node‐positive breast cancer. J. Surg. Oncol. 2012; 106:393–398. © 2012 Wiley Periodicals, Inc.