第三代芳香化酶抑制剂辅助治疗绝经后乳腺癌疗效与安全性的Meta分析

Efficacy and safety of third generation aromatase inhibitors in postmenopausal women with breast cancer:a Meta-analysis

目的系统评价第三代芳香化酶抑制剂（AIs）对乳腺癌疗效与安全性的影响。方法计算机检索Cochrane Library、PubMed、EMbase、中国生物医学文献数据库、万方数据库等,收集符合纳入标准的研究,检索时限均从建库至2014年10月,并追溯纳入研究的参考文献和手工检索相关会议资料。由2位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后,采用RevMan 5.2软件进行Meta分析。结果共纳入11个随机对照研究,Meta分析结果显示,与他莫昔芬相比,AIs初始及序贯治疗方案都能显著提高总生存率（HR=0.91,95%CI 0.84～0.99,P=0.04;HR=0.83,95%CI 0.73～0.95,P=0.008）;无病生存率在.Ms初始治疗（HR=0.86,95%CI 0.80～0.92,P〈0.01）、序贯治疗（HR=0.72,95%CI 0.64～0.99,P〈0.01）及后续强化治疗方案组（HR=0.62,95%CI0.52～0.74,P〈0.01）均有显著提高。AIs组序贯治疗方案骨折发生率略高于他莫昔芬（P=0.05）,另2种治疗方案与他昔莫芬无显著差异（P〉0.05）;AIs治疗方案子宫内膜癌发生率低于他莫昔芬（P〈0.01）;AIs单药方案血栓发生率低于他莫昔芬,而序贯方案高于他莫昔芬（P〈0.01）;AIs单药方案及序贯治疗方案心血管不良事件发生率高于他莫昔芬（P〈0.01）,而后续强化方案与他莫昔芬无显著差异（P〉0.05）。结论 AIs较他莫昔芬能带来更多的生存获益,其中序贯治疗较起始治疗方案似更有优势;AIs降低了子宫内膜癌的发病率,而骨折、血栓、心血管不良事件等药物不良反应可以预防。

Objective To system evaluate the third generation aromatase inhibitors（AIs） on breast cancer.Methods Computer retrieval of Cochrane Library,PubMed,EMbase,Chinese biomedical literature database,Wanfang database,collected studies that met the inclusion criteria,searched from inception of database to October 2014,and also searched the research references and manually searched relevant meeting abstracts.According to the inclusion and exclusion criteria,2 reviewers independently screened literature quality;Meta-analysis was carried out using RevMan 5.2 software.Results 11 randomized controlled studies were enrolled,Meta-analysis results show that,compared with tamoxifen,initial AIs and sequential treatment program can significantly improve overall survival（HR = 0.91,95%CI 0.84- 0.99,P = 0.04;HR = 0.83,95%CI 0.73-0.95,P =0.008）;disease free survival rate in AIs at the initial treatment（HR =0.86,95%CI 0.80-0.92,P〈0.01）,at sequential therapy（HR = 0.72,95%CI 0.64- 0.99,P〈0.01） and following intensive therapy regimen group（HR =0.62,95%CI 0.52-0.74,P〈0.01） had improved significantly.AIs group sequential treatment regimen fracture rate was slightly higher than that of tamoxifen（P = 0.05）,the other 2 treatment scheme showed no significant differences from tamoxifen（P〉0.05）;the incidence of endometrial carcinoma in AIs was lower than tamoxifen treatment（P〈0.01）;AIs single regimen＇ s thrombosis incidence was less than tamoxifen,and sequential scheme was higher than that of tamoxifen（P〈0.01）;AIs single agent chemotherapy and sequential treatment＇s adverse cardiovascular events incidence was higher than that of tamoxifen（P〈0.01）,and the subsequent strengthening scheme showed no significant difference from tamoxifen（P〉0.05）.Conclusion AIs can bring more survival benefit than tamoxifen,and the sequential therapy seems to be more advantages than initial treatment;AIs reduces the incidence of endometrial cancer,and need to prevent adverse reaction such as fracture,thrombosis,cardiovascular events.