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.