他莫昔芬及其代谢产物血药浓度与ER阳性乳腺癌患者子宫内膜增生的相关性研究  

Study on Correlation of Blood Concentrations of Tamoxifen and Its Metabolites with Endometrial Hyperplasia in ER-positive Breast Cancer Patients

作　　者：朱余兵[1] 赵拯[1] 刘赟心[1] 

机构地区：[1]南京医科大学附属南京医院/南京市第一医院药学部,南京210006

出　　处：《中国药房》2017年第20期2768-2771,共4页China Pharmacy

基　　金：江苏省药学会奥赛康临床药学立项课题(No.201209)

摘　　要：目的:考察他莫昔芬(TAM)及其代谢产物血药浓度与雌激素受体(ER)阳性乳腺癌患者子宫内膜增生的相关性。方法:选取2015年3月-2016年4月我院ER阳性乳腺癌患者69例,均接受TAM持续治疗半年以上(每日2次,每次1片)。根据治疗后其子宫内膜厚度分为异常增生组(40例)和正常组(29例),采用高效液相色谱-荧光法测定其体内TAM及代谢产物[4-羟基他莫昔芬(OHT)、N-去甲基他莫昔芬(DMT)和Endoxifen]的稳态血药浓度,采用Pearson检验和多元回归分析考察血药浓度等因素与子宫内膜厚度的相关性。结果:异常增生组患者的用药时间、Endoxifen稳态血药浓度均显著长于或高于正常组,差异均有统计学意义(P<0.05);而两组患者年龄,体质量指数,并发症以及TAM、OHT、DMT稳态血药浓度比较,差异均无统计学意义(P>0.05)。患者子宫内膜厚度与Endoxifen稳态血药浓度和用药时间呈正相关性(r分别为0.447、0.460,P<0.05);以子宫内膜厚度(y)为因变量,用药时间(x_1)和Endoxifen稳态血药浓度(x_2)为自变量,进行多元回归分析,得回归方程为y=2.436+0.123x_1+0.082x_2(F=12.610,r=0.526,P<0.05)。结论:Endoxifen稳态血药浓度和患者用药时间可能与子宫内膜增生有关,可为临床预测TAM致ER阳性乳腺癌患者子宫内膜异常增生提供参考。OBJECTIVE： To investigate the correlation of blood concentrations of tamoxifen （TAM） and its metabolites with endometrial hyperplasia in estrogen receptor （ER）-positive breast cancer patients. METHODS： A total of 69 patients with ER-positive breast cancer selected from our hospital during Mar. 2015-Apr. 2016 received TAM （twice a day, one tablet each time） for more than 6 months. According to endometrial thickness, they were divided into abnormal hyperplasia group （40 cases） and normal group （29 cases）. The steady state concentrations of TAM and its metabolites [4-OH-tamoxifen （OHT）, N-demethylation tamoxifen （DMT）, Endoxifen] were determined by HPLC-FLU. The correlation of blood concentration and other factors with endometrial thickness were investigated by Pearson test and multiple regression analysis. RESULTS： The medication time and Endoxifen steady state concentration in abnormal hyperplasia group were both significantly longer or higher than normal group, with statistical significance （P〈0.05）. There was no statistical significance in age, BMI, complication and steady state concentrations of TAM, OHT and DMT between 2 groups （P〉0.05）. The endometrial thickness was positively correlated with Endoxifen steady state concentration and medication time （r=0.447, 0.460,P〈0.05）. Using endometrial thickness （y） as dependent variable, medication time （x1） and Endoxifen steady state concentration （x2） as independent variable, multiple regression analysis was conducted. Multiple regression equation was calculated as follows： y=2.436＋0.123x1＋0.082x2（F=12.610,r=0.526,P〈0.05）. CONCLUSIONS： Medication time and Endoxifen steady state concentration may be related to endometrial hyperplasia, which can provide reference for predicting TAM induced endometrial abnormal hyperplasia in ER-positive breast cancer patients.

关 键 词：他莫昔芬 代谢产物 血药浓度 子宫内膜增生 用药时间 相关性 

分 类 号：R711.74[医药卫生—妇产科学] R969.1[医药卫生—临床医学]