新辅助化疗前后Ki-67的表达改变在预测不同分子分型乳腺癌化疗疗效中的作用

Prognostic significance of Ki-67 expression before and after neoadjuvant chemotherapy in different biological breast cancer phenotypes

目的 分析不同分子分型乳腺癌患者的临床病理特征,了解新辅助治疗前后Ki-67的表达变化对不同分子分型乳腺癌患者预后的预测作用.方法 回顾性分析2007年8月至2008年8月天津医科大学肿瘤医院乳腺外科收治的178例初治乳腺癌患者的临床资料,术前均经粗针吸穿刺活检证实为乳腺癌,并给予蒽环类联合紫杉类药物新辅助化疗.根据免疫组化染色结果进行分子分型,分析不同分子分型乳腺癌患者的临床病理特征以及Ki-67表达变化对不同分型乳腺癌患者预后的影响.结果 Luminal A型42例,Luminal B型78例,人表皮生长因子受体2（HER-2）过表达型22例,三阴性36例.新辅助化疗后,达到病理完全缓解（pCR）的患者27例,占15.2％,其中Luminal A型、Luminal B型、HER-2过表达型以及三阴性乳腺癌患者的pCR率分别为14.3％、10.3％、18.2％和25.0％,差异有统计学意义（P =0.040）.在Luminal A型和三阴性乳腺癌中,新辅助治疗后Ki-67表达降低的患者无病生存率明显提高（P=0.019和P=0.022）.Cox多因素分析的结果显示,临床分期、新辅助化疗的疗效、新辅助化疗后Ki-67的表达情况是影响三阴性乳腺癌患者无病生存率的独立因素（均P＜0.05）.结论 新辅助化疗后Ki-67的表达情况是影响三阴性乳腺癌患者无病生存率的独立因素.

Objective This study was conducted to analyze the Ki-67 expression before and after neoadjuvant chemotherapy and clinicopathological characteristics of different biological breast cancer phenotypes.The significance and prognostic predictive value of the changes of Ki-67 expression in different biological breast cancer phenotypes were analyzed.Methods A regression analysis was performed on 178 patients with invasive breast carcinoma who accepted neoadjuvant chemotherapy at Tianjin Medical University Cancer Institute and Hospital from August 2007 to August 2008.These patients were subtyped by hormone receptor status and HER-2 status.The Ki-67 index （percentage of Ki-67-positive cancer cell nuclei） was determined by immunohistochemistry.The prognostic value of Ki-67 index for disease-free survival （DFS） in different biological breast cancer phenotypes was analyzed using Kaplan-Meier survival and multivariable Cox regression.Results The overall pathologic CR （pCR） rate,defined as no invasive residuals in the breast and axilla,was 15.2%.The highest pCR rate of 25.0% was observed in the TNBC patients,which was 14.3%,10.3% and 18.2% in the luminal A,luminal B and HER2 overexpressing patients,respectively （P =0.040）.The changes of Ki-67 expression in pre-NAC and post-NAC patients showed a prognostic significance in luminal A and TNBC （P =0.019 and P =0.022,respectively） cases.Clinical stage,the efficacy of NAC,and changes of Ki-67 expression between pre-and post-NAC were independent prognostic factors in TNBC patients who did not achieve pCR.Conclusions The Ki-67 expression after neoadjuvant chemotherapy is an independent prognostic factor affecting the disease-free survival （DFS） in TNBC patients who have not achieved pCR.