Expression Of Chemokine Receptor CXCR4 In Locally Advanced Breast Cancer Patients With The Efficacy And Prognosis Correlation Of Neoadjuvant Chemotherapy

Background and Objective: Chemokine receptor CXCR4 is a seven transmembrane G protein-coupled receptors, currently has been confirmed to various cancers including breast cancer invasion and metastasis. CXCR4 expression and the efficiency of neoadjuvant chemotherapy for breast cancer and the relationship between prognostic factors were studied by many scholars of, but has not yet formed a unified conclusion. To seek the efficiency index of forecasting Neo-adiuvant chemotherapy, to affirm the forecast effect of CXCR4 to the therapy effect of Neo-adiuvant chemotherapy, to compare the CXCR4 expression before and after NAC,and the relationships of response and survival between high CXCR4 and low CXCR4 were analyzed,and afford the new index to forecast the therapy effect of NAC before chemotherapy.Methods: Eight-six patients withⅡb~Ⅲb stage LABC treated with 4 cycles of neoadjuvant taxanes and anthracyclines chemotherapy were included in this retrospective study. Of which 52 cases of infiltrating ductal carcinoma, 20 cases of invasive lobular carcinoma, 6 cases of pure carcinoma, 4 cases of scirrhous, 4 cases of medullary carcinoma.Expression of CXCR4 were analyzed by immunohistochemistry method, to compare the CXCR4 expression before and after NAC.The clinical and pathologic response and the relationships of response and survival between high CXCR4 and low CXCR4 were analyzed. With Chi-square test or Fisher exact test analysis of CXCR4 expression and neoadjuvant chemotherapy clinical and pathological effects, Kaplan-Meier survival analysis of patients and the log-rank test to compare survival rates, COX proportional hazards regression model to calculate the risk of recurrence and deathResults: Of the 86 patients,28(32.6%) were low CXCR4 and 58(67.4%) were high CXCR4. After neoadjuvant chemotherapy , 37(43.0%)were low CXCR4, 49(57.0%)were High CXCR4,CXCR4 showed no significant changes(χ~2=1.00,P>0.05). The overall response rate(OR) was 90.7% ( 78?86 ), including 20.9% clinical complete response(cCR) and 69.8%clinical partial response, the pathologic complete response(pCR) was15.1%.The cCR and pCR were39.3% and 28.6% in patients with low CXCR4, significantly higher than patients with high CXCR4 respectively(12.07%%and 8.6%)(P<0.05).After neoadjuvant chemotherapy, high CXCR4 had worse 5-year relapse-free survival free survival (RFS) 34% than those with low CXCR4 59% (P=0.0027).The 5-year overall survival (OS)was57 % for high CXCR4 and 68% for low CXCR4. (P=0.0139).The relative risks for recurrence and death in the high CXCR4 group were 2.923-fold (95%CI=1.418—6.023;P=0.0036) and 3.364-fold (95%CI=1.190—9.509 P=0.0221) higher, respectively than those in the low CXCR4 group. we performed a Cox proportional hazard model to further strengthen our hypothesis that high CXCR4 expression in cancer specimens following neoadjuvant chemotherapy is a novel independent prognostic indicator of poor cancer outcome in patients who have LABCConclusion: Patients with low CXCR4 were more sensitive to taxane and anthracycline neoadiuvant chemotherapy than those with high CXCR4.Patients with low CXCR4 have increased cCR and pCR rates compared with high CXCR4. After neoadjuvant chemotherapy, Low CXCR4 had a good prognosis than those with High CXCR4 .Detecting expression of CXCR4 in LABC tissue would be an important index for predicting the effects of neoadjuvant chemotherapy and as a prognosticator for LABC patients who have undergone neoadjuvant chemotherapy.