乳腺癌患者CYP2D6基因多态性对他莫昔芬疗效影响的系统评价

Effect of CYP2D6 gene polymorphism on efficacy of tamoxifen in patients with breast cancer: a systematic review

目的 系统评价CYP2D6基因多态性对他莫昔芬(Tam)参与治疗乳腺癌患者的无病生存期(DFS)和总生存期(OS)的影响,评价其作为Tam疗效预测指标及指导个体化用药的可行性。方法 计算机检索Cochrane Library、Pub Med、Embase、中国知网、中国生物医学文献数据库、维普全文数据库、万方等数据库,并手工检索相关文献,查找关于CYP2D6基因型及Tam治疗乳腺癌患者以DFS、OS为结局指标的文献。检索时间为1995年1月至2016年10月。采用Rev Man5.3软件进行Meta分析。结果 共纳入文献26篇,其中22篇为英文文献,4篇为中文文献,共包含12 602例患者。Meta分析结果显示,与未携带CYP2D6突变基因患者相比,携带CYP2D6突变基因的患者具有更短的DFS[HR=1.44,95%CI(1.18~1.76),P=0.000 3]和OS[HR=1.20,95%CI(1.07~1.35),P=0.002]。结论 乳腺癌患者经Tam治疗后,携带CYP2D6突变基因患者比未携带CYP2D6突变基因的患者具有更短的DFS和OS,可在临床使用Tam治疗前测定CYP2D6基因多态性,促进个体化给药。

AIM To evaluate the effect of CYP2D6 gene polymorphism on the disease-free survival（DFS） and overall survival（OS） of breast cancer patients treated with tamoxifen（Tam）, and evaluate its feasibility Tam as a predictor of therapeutic efficacy and guiding individualized medication. METHODS The Cochrane Library, Pub Med, Embase, CNKI, CBM, VIP and Wanfang database were searched by computer,and the relevant literature were retrieved manually. The literature about CYP2D6 genotype and DFS and OS of breast cancer patients treated as the outcome indicators with Tam were selected from January 1995 to October 2016. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS A total of 26 articles involving 12602 patients were included, 22 articles in English and 4 articles in Chinese. The meta-analysis showed that patients with the CYP2D6 mutation had shorter DFS（HR = 1.44, 95%CI（1.18-1.76）, P = 0.0003） and OS（HR = 1.20, 95% CI（1.07-1.35）, P = 0.002）. CONCLUSION The breast cancer patients with CYP2D6 mutation have shorter DFS and OS than those without CYP2D6 mutation when treated by Tam. CYP2D6 gene polymorphism can be detected before clinical use of Tam to promote individualized administration.