High chemokine receptor CXCR4 level in triple negative breast cancer specimens predicts poor clinical outcome.
BACKGROUND
Basal-like tumors or triple negative breast cancers are those that lack hormone-receptor and HER-2 expressions. They are considered to be aggressive tumors, and molecular mechanism to account for this is poorly understood. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that high CXCR4 overexpression level in cancer specimens predicts a poor outcome in patients with triple negative breast cancers.


METHODS
One hundred fifty-one patients with triple negative breast cancers were prospectively accrued and analyzed. All had undergone standardized treatment and surveillance protocols. From each specimen, CXCR4 levels were detected using Western blots. Results were quantified against 1 microg of HeLa cells (positive controls). CXCR4 expression was defined as high (>or=6-fold) or low (<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
At a median follow-up of 37 mo, patients whose tumors had high CXCR4 overexpression (>or=6-fold) had a significantly higher incidence of cancer recurrence (P=0.014) and cancer-related death (P=0.026) than those in the low CXCR4 group (<6-fold). After adjusting for tumor size and nodal status, the relative risk for cancer recurrence and death in the high CXCR4 group was 2.1-fold (P=0.007; 95% CI: 1.22 to 3.8) and 2-fold (P=0.047; 95% CI: 1.01 to 4.06) higher than those in the low CXCR4 group, respectively.


CONCLUSIONS
High CXCR4 overexpression in cancer specimens predicts a worse outcome in patients who have triple negative breast cancer.
Chu
Quyen D
QD
Department of Surgery, Louisiana State University Health Sciences Center in Shreveport and the Feist-Weiller Cancer Center, Shreveport, Louisiana 71130, USA. qchu@lsuhc.edu
Panu
Lori
L
Holm
Neal T
NT
Li
Benjamin D L
BD
Johnson
Lester W
LW
Zhang
Songlin
S
D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006367:HeLa Cells; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000235:genetics*; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4