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目的 Ki-67是细胞增殖的相关抗原,Ki-67指数是区分乳腺癌Luminal A型和Luminal B型的重要生物学指标,高Ki-67指数往往预示着不良的预后。然而在三阴性乳腺癌(triple negative breast cancer,TNBC)中,Ki-67预后价值尚不明确。本研究旨在探讨TNBC中Ki-67指数的预后价值。方法回顾性分析郑州大学附属肿瘤医院2009-01-06-2010-12-30收治的310例经病理确诊为TNBC并有完整资料和随访数据患者的临床及病理资料,分析Ki-67指数等指标对患者生存预后影响。利用SPSS 17.0软件,计数资料比较采用χ~2检验。Ki-67诊断价值及截断值采用ROC曲线进行分析。生存分析采用Kaplan-Meier法,并进行Log-rank检验。多因素分析采用Cox比例风险模型。结果中位随访时间65个月(3~81个月),310例乳腺癌患者中复发68例(21.9%),死亡49例(15.8%),其中48例死于乳腺癌(15.5%)。Ki-67指数与患者月经状态(χ~2=8.484,P=0.014)、肿瘤大小(χ~2=17.580,P=0.007)、腋窝淋巴结状态(χ~2=30.071,P<0.001)以及组织学分级(χ~2=17.626,P=0.001)均相关。低(Ki-67≤20%)、中(20%50%)5年无病生存率(disease-free survival,DFS)分别为96.5%、87.3%和64.9%,差异有统计学意义,P<0.001;5年总生存率(overall survival,OS)分别为96.5%、90.2%和75.5%,差异有统计学意义,P<0.001。Ki-67评价TNBC患者DFS及OS的ROC曲线下面积分别为0.707和0.689,Ki-67评价预后最佳截断值为57.5%。单因素分析中,Ki-67指数(χ~2=31.779,P<0.001)、肿瘤大小(χ~2=140.260,P<0.001)、腋窝淋巴结状态(χ~2=120.467,P<0.001)和组织学分级(χ~2=8.765,P=0.012)是影响TNBC患者DFS的相关因素,Ki-67指数(χ~2=18.218,P<0.001)、肿瘤大小(χ~2=299.718,P<0.001)、腋窝淋巴结状态(χ~2=68.794,P<0.001)和组织学分级(χ~2=7.572,P=0.023)是影响TNBC患者OS的相关因素;多因素分析中,Ki-67指数(HR=2.074,95%CI:1.279~3.364,P=0.003)、肿瘤大小(RR=1.879,95%CI:1.152~3.062,P=0.011)和腋窝淋巴结状态(RR=2.345,95%CI:1.825~3.015,P<0.001)是影响患者DFS的独立因素,Ki-67指数(RR=1.752,95%CI:1.020~3.008,P=0.042)、肿瘤大小(RR=20.011,95%CI:1.132~3.574,P=0.017)和腋窝淋巴结状态(RR=2.021,95%CI:1.517~2.693,P<0.001)是影响患者OS的独立因素。结论 Ki-67指数与TNBC患者预后相关,高Ki-67指数患者预后不良,Ki-67指数有望成为判断TNBC患者预后的一项重要生物学指标。
Objective Ki-67 is a cell proliferation-related antigen, Ki-67 index is an important biological indicators of breast cancer Luminal A type and Luminal B type, high Ki-67 index often indicates a poor prognosis. However, the prognostic value of Ki-67 is not yet clear in triple negative breast cancer (TNBC). This study aimed to investigate the prognostic value of Ki-67 index in TNBC. Methods The clinical and pathological data of 310 patients with pathologically diagnosed TNBC who had complete data and follow-up data were retrospectively analyzed. The Ki-67 index and other indicators were analyzed Impact on patient survival prognosis. Using SPSS 17.0 software, count data were compared using χ ~ 2 test. Ki-67 diagnostic value and cutoff value using ROC curve analysis. Survival analysis using Kaplan-Meier method, and Log-rank test. Multivariate analysis used a Cox proportional hazards model. Results The median follow-up time was 65 months (range, 3 to 81 months). Of the 310 breast cancer patients, 68 (21.9%) were recurrent and 49 (15.8%) died. Of these, 48 died of breast cancer (15.5%). The Ki-67 index was significantly correlated with the patient’s menstrual status (χ ~ 2 = 8.484, P = 0.014), tumor size (χ ~ 2 = 17.580, P = 0.007), axillary lymph node status School grade (χ ~ 2 = 17.626, P = 0.001). 5-year disease-free survival (DFS) was significantly higher in patients with high Ki-67 (Ki-67≤20%), moderate (20% Respectively, 96.5%, 87.3% and 64.9%, respectively, the difference was statistically significant (P <0.001). The 5-year overall survival was 96.5%, 90.2% and 75.5%, respectively, with significant difference <0.001. The area under the ROC curve of DFS and OS in patients with TNBC was 0.707 and 0.689 for Ki-67, and 57.5% for Ki-67. In univariate analysis, Ki-67 index (χ ~ 2 = 31.779, P <0.001), tumor size (χ ~ 2 = 140.260, P <0.001), axillary lymph node status Histological grade (χ ~ 2 = 8.765, P = 0.012) was the correlative factor of DFS in patients with TNBC. The Ki-67 index (χ ~ 2 = 18.218, 0.001). The axillary lymph node status (χ ~ 2 = 68.794, P <0.001) and histological grade (χ ~ 2 = 7.572, P = 0.023) were the related factors of OS in TNBC patients. In the multivariate analysis, the Ki- Tumor size (RR = 1.879, 95% CI: 1.152-3.062, P = 0.011) and axillary lymph node status (RR = 2.345, 95% CI: (RR = 1.752, 95% CI: 1.020 ~ 3.008, P = 0.042), tumor size (RR = 20.011, 95% CI: 1.132 ~ 3.574, P = 0.017) and axillary lymph node status (RR = 2.021, 95% CI: 1.517-2.693, P <0.001) were the independent factors influencing OS in patients. Conclusions The Ki-67 index is associated with the prognosis of patients with TNBC. The prognosis of patients with high Ki-67 index is poor. The Ki-67 index is expected to be an important biological index to judge the prognosis of TNBC patients.