Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy，NCT）疗效和预后的影响，探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response，pCR）之间的关系。临床病理参数与疗效分析用χ2检验，影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174，P=0.002）和PR（r=－0.132，P=0.019）呈负相关，与HER2（r=0.140， P=0.012）和乳腺肿瘤大小（r=0.132，P=0.019）呈正相关；ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%，χ2=22.761，P=0.000）；PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%，χ2=7.950，P=0.005）；Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552，P=0.033）；化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356，P=0.000）；各分子亚型间化疗疗效差异显著，Luminal A型pCR率为1.4%（1/71），Luminal B型pCR率为15.3%（25/163），HER2过表达型pCR率为31.3%（14/45），三阴性型pCR率为22.0%（9/41）（χ2=20.639，P=0.000）；用Kaplan-Meier法进行生存分析，Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组，两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感，但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标，Ki-67指数与ER、PR、HER2之间存在相关性。

The correlationship of Ki-67 with clinical pathological characteristics and efficacy of neoadjuvant chemotherapy in breast cancer

Objective To analyze the impact of clinical pathological factors on efficacy and prognosis of primary breast cancer patients treated with neoadjuvant chemotherapy (NCT), and explore the predictive factors affecting the efficacy of neoadjuvant chemotherapy in breast cancer. Method A total of 320 patients with locally advanced breast cancer were enrolled in this study. And the status of cancer tissue ER, PR, HER2 and Ki-67 in these patients were retrospectively reviewed. The patients received surgery after 4-6 cycles of NCT. We analyzed the relationship be-tween clinical pathological characteristics and pathologic complete response(pCR). Parameter of clinical pathological and analysis of curative effect were performed by χ2 test. Prognostic factors were determined by COX multivariate re-gression. Result Ki-67 index negatively correlated with ER (r=-0.174, P=0.002)/PR (r=-0.132, P=0.019) expres-sion. Higher Ki-67 index was associated with larger tumor size (r=0.132, P=0.019) and HER2 overexpression (r=0.140, P=0.012). pCR rate was higher in ER/PR negative patients than ER/PR positive patients (respectively 26.9%vs 7.4%, χ2=22.761, P=0.000; 22.7% vs 10.9%; χ2=7.950, P=0.005 ). patiens with Ki-67 high expression had higher pCR rate than those with Ki-67 low expression, (18.0% vs 8.6%, χ2=4.552, P=0.033). patiens with Ki-67 decreased group after neoadjuvant chemotherapy got higher pCR rate than those Ki-67 undecreased group, (19.8% vs 1.3%, χ2=15.356, P=0.000). Molecular subtype exerted a differential effect on response to NCT. Patients in Luminal A got low-er pCR rate 1.4% (1/71). Compared with Luminal B 15.3% (25/163), HER2 overexpression subtype 31.3% (14/45), and triple-negative phenotype 22.0% (9/41). (χ2=20.639, P=0.000). Patients with Ki-67 low expression had longer DFS (P=0.034) and OS (P=0.034) than those with Ki-67 high expression. Conclusion Ki-67 high expression corre-lated with better response to NCT but worse prognosis. Ki-67 expression and Ki-67 change after chemotherapy are in-dependent prognostic(DFS)factors. ER, PR, Ki-67 and molecular subtype may be the predictive factors of NCT effect. Ki-67 index associated with ER, PRand HER2.