雌激素受体阳性乳腺癌患者内分泌治疗期高脂血症的临床特征及中药用药分析:基于真实世界研究

Clinical Characteristics and Traditional Chinese Medicine of Hyperlipidemia in Estrogen Receptor Positive Breast Cancer Patients during Endocrine Therapy:a Real World Study

背景乳腺癌是全球发病率最高的恶性肿瘤,内分泌治疗可降低体内雌激素水平,进而影响患者的血脂水平,降低患者的生活质量和治疗依从性。目的分析真实世界雌激素受体阳性乳腺癌患者内分泌治疗期高脂血症的临床特征及中药处方用药规律。方法基于回顾性研究的方法,选择在山东中医药大学附属医院2012年1月—2022年3月接受内分泌治疗的雌激素受体阳性乳腺癌患者238例为研究对象。通过科研大数据搜索平台导出数据,包括患者的年龄、三酰甘油、总胆固醇、低密度脂蛋白、内分泌治疗药物、中药处方等,建立患者临床资料数据表。根据内分泌治疗期血脂水平将基线血脂正常的雌激素受体阳性乳腺癌患者分为血脂正常组和血脂异常组,同时将血脂异常中高脂血症分为高胆固醇血症、高甘油三酯血症和混合型高脂血症。使用中医传承辅助平台“方剂分析”对导出的处方进行频次、四气、五味、归经、用药规律的分析,通过“新方分析”获取新处方。结果238例雌激素受体阳性乳腺癌患者中基线血脂正常的患者97例(40.8%),其中42例(回访205人次)患者在行规范化内分泌治疗过程中出现血脂异常;血脂异常患者中51~60岁年龄段发病人次占比最多,为37.6%(77/205);血脂异常患者接受依西美坦治疗占比最高,为42.0%(86/205)。42例(回访205人次)基线血脂正常的雌激素受体阳性乳腺癌患者中107人次内分泌治疗期出现血脂异常,其中99人次出现高脂血症,以高胆固醇血症最多见49.5%人次(49/99);三种高脂血症患者的年龄比较,差异无统计学意义(P>0.05);三种高脂血症患者内分泌治疗药物种类比较,差异有统计学意义(P<0.05)。中医临床治疗雌激素受体阳性乳腺癌患者内分泌治疗期高脂血症中药处方总计为189种中药,用药频次最高的为甘草(408次);使用频率最高的为补气药(22.6%);大数据平台收集的中药归经主要分布在脾、肺、肝经等,药性主要为寒、平、温,药味主要为甘、苦、辛;“黄芪-甘草”组合频次最高;通过复杂系统熵聚类的分析,得到6个核心药物组合及3个新处方。结论雌激素受体阳性乳腺癌患者内分泌治疗期高脂血症的高发年龄为51~60岁,以高胆固醇血症最为多见。雌激素受体阳性乳腺癌患者内分泌治疗期高脂血症的病位在脾,用药主要为健脾祛湿、益气和中之品。

Background Breast cancer is the most prevalent malignancy in the world.Endocrine therapy reduces the level of estrogen in vivo,thus affecting the blood lipid level,which reduces the quality of life and the treatment compliance of patients.Objective To analyze the clinical characteristics and traditional Chinese medicine(TCM)prescription of hyperlipidemia in estrogen receptor(ER)positive breast cancer patients during endocrine therapy in real world.Methods Based on method of retrospective study,a total of 238 patients with ER positive breast cancer who received endocrine therapy in Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2012 to March 2022 were selected as the study subjects.The data including age,triglyceride,total cholesterol,low density lipoprotein,endocrine therapy drugs,TCM prescriptions of the patients were exported through the search platform of scientific research big data to establish a clinical data table of the patients.ER positive breast cancer patients with normal baseline blood lipid levels were divided into the normal group and dyslipidemia group according to the blood lipid levels during endocrine therapy,and hyperlipidemia was classified into hypercholesterolemia,hypertriglyceridemia and mixed hyperlipidemia.The exported prescriptions were analyzed for frequency,four properties,five flavors,channel tropism and medication regularity by using the"prescription analysis",an auxiliary platform for TCM inheritance,to obtain new prescriptions.Results Among 238 ER positive breast cancer patients,97 patients(40.8%)had normal baseline blood lipid levels,of whom 42 patients(205 person-time return visit)developed dyslipidemia during standardized endocrine therapy.Among the patients with dyslipidemia,37.6%(77/205)occurred in the age group of 51 to 60 years as the highest number;86 person-time with dyslipidemia received exemestane treatment,accounting for the highest proportion of 42.0%.Among the 42 patients with dyslipidemia(205 person-time return visit),hyperlipidemia occurred in 99 person-time,and hypercholesterolemia occurred in 49.5%(49/99).There was no statistically significance difference in the age of patients with three types of hyperlipidemia(P>0.05).There were statistically significance differences in the proportion of endocrine therapy types among patients with three types of hyperlipidemia(P<0.05).There were 189 kinds of TCM prescriptions for hyperlipidemia in ER positive breast cancer patients during endocrine treatment,licorice was the most frequently used medicine(408 times),the highest frequency of use was tonifying qi drug(22.6%).The channels of TCM collected by the big data platform were mainly distributed in the spleen,lung and liver channels.The properties of TCM were mainly cold,flat and warm,and the flavors were mainly sweet,bitter and pungent.The combination of"Astragalus and Licorice"had the highest frequency.Six core drug combinations and three new prescriptions were obtained through complex system entropy clustering analysis.Conclusion The highest incidence of hyperlipidemia in ER positive breast cancer patients during endocrine therapy is 51-60 years old,and hypercholesterolemia is the most common.The position of hyperlipidemia in ER positive breast cancer patients during endocrine therapy is in the spleen.The medication are maily used for invigorating spleen to remove dampness,tonifying qi and regulating stomach.