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Abstract：
BACKGROUND: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease.
METHODS: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5.
RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]).
CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.
METHODS: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5.
RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]).
CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.
摘要：
背景：我们的目的是研究趋化因子受体表达与新辅助化疗（NAC）反应以及局部晚期三阴性乳腺癌（TNBC）患者预后之间的任何可能关联。
方法：使用CCR5，CCR7，CXCR4和CXCR5的特异性抗体对手术标本（n=63）的档案组织进行染色后，用免疫组织化学检查趋化因子受体的表达。
结果：在肿瘤上具有高CCR5，CCR7，CXCR4和CXCR5表达和在肿瘤浸润淋巴细胞（TIL）上具有高CXCR4表达的患者与其他患者相比，具有病理完全反应（pCR）或0-I类RCB指数的可能性较小。残留淋巴结转移（ypN阳性）的患者，高CCR5TM（肿瘤），与其他相比，高CXCR4TM表达的风险比（HR）增加（DFS：HR=2.655[1.029-6.852]；DSS：HR=2.763[1.008-7.574]），（DFS：HR=2.036[0.805-5.148]；DSS：HR=2.689[1.020-7.090]），和（DFS：HR=2.908[1.080-7.829]；DSS：HR=2.132（0.778-5.846）），分别。然而,与CXCR5TIL患者相比,无CXCR5TIL表达患者的HR增加(DFS:2.838[1.266-6.362];DSS:4.211[1.770-10.016]).
结论：发现CXCR4TM和CCR5TM的高表达与不良预后有关，和CXCR5TM与本队列中局部晚期TNBC的化疗反应差相关。我们的结果表明，TNBC患者可以从包含新辅助化疗方案的趋化因子受体抑制剂治疗中受益。
方法：使用CCR5，CCR7，CXCR4和CXCR5的特异性抗体对手术标本（n=63）的档案组织进行染色后，用免疫组织化学检查趋化因子受体的表达。
结果：在肿瘤上具有高CCR5，CCR7，CXCR4和CXCR5表达和在肿瘤浸润淋巴细胞（TIL）上具有高CXCR4表达的患者与其他患者相比，具有病理完全反应（pCR）或0-I类RCB指数的可能性较小。残留淋巴结转移（ypN阳性）的患者，高CCR5TM（肿瘤），与其他相比，高CXCR4TM表达的风险比（HR）增加（DFS：HR=2.655[1.029-6.852]；DSS：HR=2.763[1.008-7.574]），（DFS：HR=2.036[0.805-5.148]；DSS：HR=2.689[1.020-7.090]），和（DFS：HR=2.908[1.080-7.829]；DSS：HR=2.132（0.778-5.846）），分别。然而,与CXCR5TIL患者相比,无CXCR5TIL表达患者的HR增加(DFS:2.838[1.266-6.362];DSS:4.211[1.770-10.016]).
结论：发现CXCR4TM和CCR5TM的高表达与不良预后有关，和CXCR5TM与本队列中局部晚期TNBC的化疗反应差相关。我们的结果表明，TNBC患者可以从包含新辅助化疗方案的趋化因子受体抑制剂治疗中受益。
