Overexpression of chemokine receptor CXCR4 in cancer specimens following neoadjuvant chemotherapy predicts outcome in patients with locally advanced breast cancer (LABC)

Abstract

10578 Background: Despite significant advances made in the treatment of locally advanced breast cancer (LABC) with neoadjuvant chemotherapy, a significant number of patients continue to die. A molecular predictor to identify those who are at an increased risk for relapse is sorely needed. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that CXCR4 overexpression levels in cancer specimens following neoadjuvant chemotherapy predict cancer outcome in patients with LABC. Methods: 54 patients with LABC were prospectively accrued and analyzed. All had neoadjuvant chemotherapy, followed by definitive surgical and adjuvant chemo-radiation therapy. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. A 1 cm 3 cancer from the surgical specimens of each patient was retrieved for analysis. CXCR4 levels were detected using Western blots and results were quantified against 1 μg of HeLa cells (positive controls). CXCR4 expression was defined as low (<6.6 fold) or high (= 6.6 fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model. Results: With a median follow-up of 30 months, patients whose tumors had high CXCR4 overexpression (= 6.6 fold) had a statistically significantly higher incidence of recurrence (p= 0.0009) and cancer-related death (p= 0.0168) than those in the low CXCR4 group (< 6.6 fold). After adjusting for tumor size, nodal status, ER, PR and HER-2 status, the relative risk for recurrence and death in the high CXCR4 group was 27.3-fold (p=0.001; 95% CI: 6.2 to 120.8) and 4.8-fold (p=0.0076; 95% CI: 1.5 to 15.0) higher than those in the low CXCR4 group, respectively. Conclusion: High CXCR4 overexpression in cancer specimens following neoadjuvant chemotherapy was highly predictive of cancer recurrence and cancer death in patients with LABC. No significant financial relationships to disclose.