Expression And Significance Of CCR4and CCR7in Different Molecular Subtypes Of Breast Cancer

Objective: To investigate the relationship between the expression ofC-C chemokine receptor4(CCR4) and C-C chemokine receptor7(CCR7) andclinicopathological features as well as clinical outcome among breastcancer subgroups (triple-negative breast cancer (TNBC), HER-2over-expression breast cancer and Lumina breast cancer).Methods: The expression of CCR4and CCR7in TNBC, HER-2over-expression breast cancer, TNBC paracancerous tissues and mammarygland benign tumor (38cases each for the4groups) and40cases of Luminabreast cancer were assessed by immunohistochemical technology.Results:1. The rate of CCR4and CCR7expression in TNBC, HER-2over-expressionbreast cancer, luminal breast cancer, TNBC paracancerous tissues andmammary gland benign tumor were47.4%,42.1%,17.5%,10.5%,13.2%,respectively(P<0.001) and50.0%,42.1%,27.5%,18.4%,15.8%,respectively(P=0.003), the difference were statistically significant.2. The expression of CCR4and CCR7in breast cancer tissue was positiverelationship（r=0.322，P＜0.001）.3. In triple-negative breast cancer cohort, CCR4high-expressioncorrelated with axilla lymph node transfer（P=0.006），tumor size（P=0.023），tumor stage(P=0.016) and distance transfer(p=0.028); CCR7high-expression correlated with axilla lymph node status（P=0.038）;patients with CCR4and CCR7high-expression tumors had lower overallsurvival(OS) rates compared with CCR4and CCR7low-expression groups(pvalue <0.001and0.004, respectively); patients with CCR7high-expressiontumors had lower disease free survival(DFS) rates compared with CCR7 low-expression groups(P=0.003); CCR4high-expression correlated withrisk of cancer-relative death (P=0.030); axilla lymph node transfercorrelated with risk of cancer recurrence(P=0.007); Multivariateanalysis showed that CCR4expression is a significant independentprognostic factor for OS（P=0.022）; axilla lymph node transfer is asignificant independent prognostic factor for DFS （P=0.025）, thedifference were statistically significant.4. In HER-2over-expression breast cancer cohort, CCR4high-expressioncorrelated with axilla lymph node transfer（P=0.002），tumor stage（P<0.001）and distance transfer(p=0.001); patients with CCR4high-expressiontumors had lower OS and DFS rates compared with CCR4low-expression groups(p value <0.001and <0.001, respectively); Tumor size and tumor stagecorrelated with risk of cancer-relative death (p value0.029and0.029,respectively); axilla lymph node transfer, tumor size and tumor stagecorrelated with risk of cancer recurrence (p value0.018,0.003and0.003,respectively), the difference were statistically significant.5. In Lumina breast cancer cohort, the expression of CCR4and CCR7werenot correlated with clinicopathological features as well as clinicaloutcome (OS and DFS).6. In molecular subtypes of breast cancer cohort, the number of internalorgan metastases higher than the number of bone metastases in the rateof CCR4and CCR7high-expression group. The difference was notstatistically significant（P>0.05）.Conclusions:In triple-negative breast cancer cohort, the high-expression of CCR4and CCR7influences tumor growth, metastasis and prognosis. CCR4expression and axilla lymph node transfer were a potential independentprognostic factor for TNBC patients OS and DFS, respectively. CCR4high-expression predicted poor OS and DFS for HER-2over-expression breast cancer patients. The expression of CCR4and CCR7were notcorrelated with patients with Lumina breast cancer clinical outcome.