乳腺癌辅助内分泌治疗对肝功能影响的真实世界研究  

A real-world study of the effects of endocrine therapy on liver function in breast cancer

作　　者：李玥翀 邓梓禧 汪颖姣 徐涛[2] 孙强[1] 沈松杰 Li Yuechong;Deng Zixi;Wang Yingjiao;Xu Tao;Sun Qiang;Shen Songjie(Department of Breast Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of Epidemiology and Biostatistics,Institute of Basic Medical Sciences,Peking Union Medical College,Chinese Academy of Medical Sciences&School of Basic Medicine,Beijing 100730,China)

机构地区：[1]中国医学科学院、北京协和医学院、北京协和医院乳腺外科,北京100730 [2]中国医学科学院基础医学研究所、北京协和医学院基础学院流行病与卫生统计学系,北京100730

出　　处：《中华外科杂志》2023年第2期107-113,共7页Chinese Journal of Surgery

基　　金：中央高水平医院临床科研业务费项目(2022-PUMCH-B-038);国家自然科学基金(52173149);北京市自然科学基金(7222129)。

摘　　要：目的探讨不同内分泌治疗药物对早期乳腺癌患者肝功能的影响。方法采用回顾性队列研究方法,纳入2013年1月1日至2021年12月31日在北京协和医院接受辅助内分泌治疗的4318例早期乳腺癌患者,均为女性,年龄(51.2±11.3)岁(范围:20~87岁)。根据药物治疗方案分组,阿那曲唑组1182例,来曲唑组592例,依西美坦组332例,托瑞米芬组2212例。记录患者在治疗前,服药6、12、18、24、36、48、60个月和停药后1年的肝功能水平,使用混合效应模型比较3种芳香化酶抑制剂(阿那曲唑、来曲唑、依西美坦)和托瑞米芬对肝功能的影响。结果4组患者用药6个月时ALT、AST均较治疗前上升(P值均<0.01),停药1年后各组的总胆红素、直接胆红素、AST较治疗前无明显差异(P值分别为0.538、0.718、0.061)。各组间AST的变化无差异(F=2.474,P=0.061)。3种芳香化酶抑制剂组间ALT的变化无差异(阿那曲唑比来曲唑,P=0.182;阿那曲唑比依西美坦,P=0.535;来曲唑比依西美坦,P=0.862)。阿那曲唑、来曲唑对ALT的影响高于托瑞米芬(P<0.01、P=0.009)。各组在用药6个月时均出现肝功能异常患者,随用药时间延长,异常例数均呈下降趋势。结论3种芳香化酶抑制剂(阿那曲唑、来曲唑、依西美坦)和托瑞米芬都可使患者ALT、AST水平明显上升,停药1年后各指标可逐渐恢复至治疗前,非甾体类芳香化酶抑制剂(阿那曲唑、来曲唑)对ALT的影响大于托瑞米芬。Objective To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer.Methods A retrospective cohort study was conducted to include 4318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery,Peking Union Medical College Hospital from January 1,2013 to December 31,2021.All the patients were female,aged(51.2±11.3)years(range:20 to 87 years),including 1182 patients in the anastrozole group,592 patients in the letrozole group,332 patients in the exemestane group,and 2212 patients in the toremifene group.The mixed effect model was used to analyze and compare the liver function levels of patients at baseline,6,12,18,24,36,48,60 months of medication,and 1 year after drug withdrawal among the three aromatase inhibitors(anastrozole,letrozole,exemestane)and toremifene.Results ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months(all P<0.01),and there were no significant differences in total bilirubin,direct bilirubin and AST levels among all groups one year after drug withdrawal(P:0.538,0.718,0.061,respectively).There was no significant difference in the effect of all groups on AST levels(F=2.474,P=0.061),and in the effect of three aromatase inhibitors(anastrozole,letrozole,and exemestane)on ALT levels(anastrozole vs.letrozole,P=0.182;anastrozole vs.exemestane,P=0.535;letrozole vs.exemestane,P=0.862).Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene(P<0.01,P=0.009).The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline,and then the proportion showed a decreasing trend over time.Conclusions Three aromatase inhibitors(anastrozole,letrozole,and exemestane)and toremifene can significantly increase the level of ALT and AST in patients with breast cancer,and the levels can gradually recover to the baseline after 1 year of drug withdrawal.The effect of non-steroidal aromatase inhibitors(anast

关 键 词：乳腺肿瘤 肝功能不全 内分泌治疗 阿那曲唑 来曲唑 依西美坦 托瑞米芬 

分 类 号：R737.9[医药卫生—肿瘤]