局部进展期乳腺癌趋化因子受体CXCR4的表达与新辅助化疗疗效的相关性及预后研究  

Expression of chemokine receptor CXCR4 in locally advanced breast cancer patients with the efficacy and prognosis correlation of neoadjuvant chemotherapy

作　　者：杨永德[1] 印国兵[1] 曾晓华[1] 

机构地区：[1]重庆医科大学附属第二医院普外科,重庆400010

出　　处：《中国癌症杂志》2011年第6期446-451,共6页China Oncology

摘　　要：背景与目的:目前已经确立新辅助化疗在局部进展期乳腺癌(local advanced breast cancer,LABC)治疗中的地位,达到病理完全缓解者可提高生存率,但仍有大量患者复发、死亡,而无法从中受益。因此,我们迫切需要从分子水平找到可以预测新辅助化疗效果和预后的指标。目前已经证实趋化因子受体CXCR4与乳腺癌的侵袭和转移有关,然而关于CXCR4能否作为LABC患者新辅助化疗中的疗效指标和预后指标,目前却鲜有报道。本研究中,我们采用紫杉醇联合蒽环类的新辅助化疗方案治疗LABC,同时比较CXCR4低表达和高表达与疗效和远期生存的相关性。方法:对接受4个周期紫杉醇联合蒽环类的新辅助化疗方案进行治疗的86例ⅡB～ⅢB期(参照2002年AJCC乳腺癌TNM分期标准)LABC患者资料进行回顾性分析。用免疫组织化学法检测新辅助化疗前后乳腺癌组织CXCR4的表达,分析新辅助化疗对CXCR4低表达和CXCR4高表达患者的临床、病理疗效及其与远期生存的关系。结果:86例患者中58例(67.4%)为CXCR4高表达,28例(32.6%)为CXCR4低表达,新辅助化疗后,CXCR4高表达49例(57.0%),低表达37例(43.0%),化疗前后差异无统计学意义(P>0.05)。86例患者的肿瘤原发灶总有效率(ORR)为90.7%(78/86),其中临床完全缓解(cCR)占20.9%(18/86),部分缓解(PR)占69.8%(60/86),病情稳定(SD)占9.3%(8/86),病理完全缓解(pCR)占15.1%(13/86)。CXCR4低表达cCR为39.3%(11/28),pCR为28.6%(8/28),明显高于CXCR4高表达的cCR[12.07%(7/58)]和pCR[8.6%(5/58)](P<0.05)。新辅助化疗后,LABC患者CXCR4高表达的复发和死亡的相对风险分别是CXCR4低表达的2.923(95%CI:1.418～6.023,P=0.003 6)倍和3.364(95%CI:1.190～9.509,P=0.022 1)倍。CXCR4高表达5年无复发生存率(RFS)为34%,低于CXCR4低表达组(59%)(P=0.002 7),CXCR4高表达5年总体生存率(OS)为57%,低于CXCR4低表达组(68%)(P=0.013 9)。COX回归分析显示,高表达的CXCR4是LABC患者在新辅助化疗后一�Background and purpose:The effectiveness of neoadjuvant chemotherapy(NAC) in locally advanced breast cancer(LABC) has been proved and that pathologic complete response(pCR) after NAC could improve survival has been proved either.Regardless of treatment,the majority of patients with LABC continues to recur and die from this disease.A molecular predictor to predict the effect of NAC and identify at-risk patients is sorely needed.CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis,but the mechanism of it's translating into clinical practice is still unclear.No study to date has examined the expression of CXCR4 as an indicator of the efficacy of NAC as a prognosticator for LABC patients who have undergone NAC.Therefore,we used taxanes and anthracyclines for LABC and compared the expression of CXCR4 before and after chemotherapy and the relationship of effectiveness and survival.Methods:Eighty-six patients with Ⅱb–Ⅲb stage LABC treated with 4 cycles of neoadjuvant taxanes and anthracyclines chemotherapy were included in this retrospective study.Expression of CXCR4 was analyzed by immunohistochemistry method.The clinical and pathologic response to neoadjuvant taxanes and anthracyclines chemotherapy,and the relationships of response and survival between high CXCR4 and low CXCR4 patients were analyzed.Results:Of the 86 patients,28(32.6%) with low the CXCR4 expression and 58(67.4%) with high CXCR4 expression.After NAC,37(43.0%) had low CXCR4 expression,49(57.0%) had high CXCR4 expression,which showed no significant changes(P>0.05).The overall response rate(ORR) was 90.7%(78/86),including 20.9% clinical complete response(cCR) and 69.8% clinical partial response,and the pathologic complete response(pCR) was 15.1%.The cCR and pCR were 39.3% and 28.6% in patients with low CXCR4,significantly higher than that in patients with high CXCR4 respectively(12.07% and 8.6%)(P<0.05).After NAC,the relative risks for recurrence and death in the high CXCR4 group were 2.923-fold(95%CI: 1.418–

关 键 词：乳腺癌 趋化因子受体 CXCR4 新辅助化疗 

分 类 号：R73[医药卫生—肿瘤]