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.
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).


CONCLUSIONS
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.
Mizell
Jason
J
Department of Surgery, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA.
Smith
Mark
M
Li
Benjamin D L
BD
Ampil
Fred
F
Chu
Quyen D
QD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D019718:Receptors, CXCR4; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C527276:CXCR4 protein, human