CXCR4 as a predictive marker for locally advanced breast cancer post-neoadjuvant therapy.
BACKGROUND
CXCR4 is a G-protein coupled receptor that has been linked with metastasis in several cancers, including breast cancer. We recently demonstrated that high CXCR4 levels in primary tumors of patients with breast cancer had a prognostic significance. We hypothesize that patients whose tumors had a low CXCR4 overexpression level following neoadjuvant chemotherapy will have a lower recurrence rate than those whose tumors remained high.


METHODS
Seventeen locally advanced breast cancer (LABC) patients were accrued, and tumor specimens were obtained before and after neoadjuvant therapy. CXCR4 levels were quantified by Western blots against 1 μg of protein from HeLa cells. The primary end-point was cancer recurrence. Statistical tests utilized include Kaplan-Meier survival analysis and log-rank test. A P value ≤ 0.05 was considered significant.


RESULTS
We previously defined low CXCR4 overexpression as ≤6-fold elevation and high overexpression as >6-fold elevation over HeLa cells. Of 17 LABC tumors evaluated, 10 (59%) remained in the low group, 5 (29%) reduced from high to low overexpression, and 2 (12%) maintained a high overexpression after neoadjuvant therapy. With a median follow-up of 28 mo, patients whose tumors maintained a high CXCR4 overexpression level after neoadjuvant therapy had a significantly higher rate of cancer recurrence (P = 0.0068).


CONCLUSIONS
CXCR4 was a predictive molecular marker of response to neoadjuvant chemotherapy for patients with LABC. Patients whose tumors had a persistently high CXCR4 overexpression level after neoadjuvant therapy are at a significant risk for recurrence, and therefore, should be targeted for more intensive and/or novel therapy.
Hiller
David J
DJ
Department of Surgery, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana 71130, USA.
Li
Benjamin D L
BD
Chu
Quyen D
QD
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D015409:Mastectomy, Radical; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality; D011237:Predictive Value of Tests; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors
D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4