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  • Title: Overexpression of CXCR4 in primary tumor of patients with HER-2 negative breast cancer was predictive of a poor disease-free survival: a validation study.
    Author: Mizell J, Smith M, Li BD, Ampil F, Chu QD.
    Journal: Ann Surg Oncol; 2009 Oct; 16(10):2711-6. PubMed ID: 19593633.
    Abstract:
    BACKGROUND: Although HER-2 negative tumors are thought to be less aggressive than their counterpart, there is a subset that behaves poorly. The molecular mechanism to account for this is unknown. The chemokine receptor CXCR4 is often upregulated in a wide array of cancers. Using a training dataset, we previously reported that high CXCR4 overexpression portends a poor outcome among patients with HER-2 negative breast tumors. This study aims to validate these findings, using our validation dataset. METHODS: There were 115 patients with stages I-III, HER-2 negative breast cancers who were prospectively accrued and analyzed. CXCR4 levels from primary tumors were detected using Western blots, and results were quantified against 1 microg of HeLa cells. CXCR4 expression was defined as low (<6.6 fold) or high (> or =6.6 fold). Primary endpoint was cancer recurrence. Statistical analysis performed included Spearman correlation, Fisher exact test, Kaplan-Meier survival analysis, Cox proportional hazard ratio model, and log-rank test. RESULTS: There were 13 patients in the high (> or =6.6 fold) and 102 patients in the low CXCR4 group (<6.6 fold). Overall survival (OS) and disease-free survival (DFS) for the cohort was 84 and 71%, respectively. The 5-year OS for the high CXCR4 group was 52% and for the low CXCR4 group was 86% (P = 0.08). The 5-year DFS for the high CXCR4 and low CXCR4 group was 38 and 74%, respectively (P = 0.01). CONCLUSION: We validated that high CXCR4 overexpression in primary tumors of patients with HER-2 negative tumors portend a poor outcome. These findings should be confirmed with either a prospective clinical trial and/or an external validation study.
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