2015 年第 3 期 第 13 卷

Ki67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

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关键词：乳腺癌新辅助化疗Ki67病理完全缓解预后因素预测因素

• 摘要：
• 【摘要】【摘要】目的 分析乳腺癌临床病理特征对新辅助化疗（NCT）疗效和预后的影响，探讨NCT疗效的预测因素。方法 用免疫组织化学方法检测320例早期或局部晚期乳腺癌患者癌组织ER、PR、HER2及Ki67表达状况。行NCT 4至6周期后手术。分析临床病理特征与病理完全缓解率（pCR）之间的关系。临床病理参数与疗效分析用X2检验，影响预后因素用COX多因素回归分析。结果 Ki67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或PR阴性组pCR率显著高于ER或PR阳性组（分别为26.9%:7.4%, X2=22.761，P=0.000.22.7%:10.9%,X2 =7.950，P=0.005）；Ki67高表达组pCR率18.0%(41/228) 优于Ki67低表达组8.6%(8/92)，X2 =4.552，P=0.033；化疗后Ki67表达下降组pCR率19.8%(48/243)优于未下降组1.3%(1/77)，X2=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)，X2 =20.639，P=0.000；用Kaplan-Meier法进行生存分析，Ki67低表达组无病生存时间（DFS)和总生存时间（OS）均优于Ki67高表达组，两者均为P=0.034。结论 Ki67高表达患者对化疗更敏感，但预后较差。化疗前Ki67的表达和化疗后Ki67变化是影响DFS独立的预后因素。ER、PR、Ki67及分子分型可以作为NCT疗效的预测指标，Ki67与ER、PR、HER2之间存在相关性。
• 【Abstract】 Purpose To analyze the effect of clinical and pathological factors for primary breast cancer on efficacy and prognosis of neoadjuvant chemotherapy（NCT）,and explore the predictive factors affecting the efficacy of neoadjuvant chemotherapy in breast cancer. Methods A total of 320 patients with early-stage or local advanced breast cancer were enrolled in this study. Examining the state of cancer tissues ER, PR, HER2 and Ki67 in these patients.The patients received surgery after 4-6 cycles of NCT.analyzing the relationship between clinical pathological characteristics and pathologic complete response（pCR）. Parameter of clinical pathological and analysis of curative effect were tested by X2.prognostic factors were analyzed by COX multivariate regression. Results Higher Ki67 expression indices were associated with ER-(r=-0.174,P=0.002)/PR- (r=-0.132,P=0.019)tumors,and bigger tumor size(r=0.132,P=0.019),More 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%, 22.7%vs.10.9%, X2=22.761,P=0.000,X2=7.950,P=0.005）.patiens with Ki67 high expression had higher pCR rate than those with Ki67 low expression,(18.0%vs.8.6%, X2=4.552,P=0.033).patiens who Ki67 decreased group after neoadjuvant chemotherapy got higher pCR rate than those Ki67 undecreased group,(19.8%vs.1.3%, X2=15.356,P=0.000).Patients in different molecular subtypes had different effect from chemotherapy.Patients in Luminal A got lower pCR rate 1.4%(1/71). comparent with Luminal B15.3%(25/163),HER2 subtype31.3%(14/45),and triple-negative phenotype22.0%(9/41). (X2=20.639,P=0.000). Patients with Ki67 low expression had longer DFS than those with Ki67 high expression (P=0.034), and similar in OS (P=0.034). Conclusion The patients with Ki67 over expression are more sensitive to NCT, but poor outcome. Chemotherapy before the expression of Ki67 and Ki67 change after chemotherapy are Independent prognostic（DFS）factors. ER, PR, Ki67 and molecular subtype may be the predictive factors of NCT effect. Ki67 associate with ER, PRand HER2.