Clinical Research On The Correlation Between Anthracycline-induced Cardiotoxicity And TCM Syndromes And The Prevention And Treatment Of TCM

Purpose:To study the relationship between traditional Chinese medicine syndromes and modern molecular typing of breast cancer,and the correlation between traditional Chinese medicine syndromes of breast cancer and anthracycline cardiotoxicity,so as to provide theoretical basis for the prevention and treatment of anthracycline-induced cardiotoxicity by integrated traditional Chinese and Western medicine.To evaluate the clinical efficacy of traditional Chinese medicine injection in the prevention and treatment of anthracycline-induced cardiotoxicity by meta-analysis.Material and method:1.All data including age,tumor diameter,clinical stage,expression of ER,PR,HER2,Ki67,whether combined radiotherapy,diabetes history,hypertension history,body mass index(BMI),abnormal electrocardiogram,cumulative dose of anthracycline drugs,LVEF,CK,CK-MB before and after chemotherapy from 152 cases diagnosed by pathology in oncology department of former Shenyang Military Region General Hospital from October 2016 to October 2018 were collected.Under the guidance of two deputy directors of the hospital,breast cancer was classified into four types:liver qi stagnation type,toxic heat accumulation type,qi and blood deficiency type,liver and kidney Yin deficiency type according to the TCM syndrome differentiation criteria of breast cancer in"Guidelines for TCM Diagnosis and Treatment of Malignant Tumors"(2014)by Professor Hongsheng Lin of Guang'anmen Hospital,Chinese Academy of Traditional Chinese Medicine.According to the molecular typing criteria of breast cancer determined by the 12th St Gallen International Breast Cancer Conference,the molecular typing of breast cancer was divided into Luminal A,Luminal B,Her-2 amplification and triple negative type.Patients were divided into two groups according to abnormal ECG and normal ECG group.SPSS22.0 is used for data analysis,chi-square test is used for counting data,paired t-test is used for index changes before and after chemotherapy,and logistics regression analysis is used for influencing factors of abnormal changes in ECG.P<0.05 was considered statistically significant.The correlation between TCM syndromes and molecular typing of breast cancer and pathological characteristics of breast cancer is analyzed.The correlation between abnormal changes of electrocardiogram induce by anthracyclines and the above factors isanalyzed.The correlation between TCM syndromes of breast cancer and cardiotoxicity induce by anthracyclines is discussed.2.Pubmed,Medline,Cochrane,CNKI and Wan Fang electronic databases are used for literature retrieval,and manual retrieval was conducted in the library of liaoning university of traditional Chinese medicine.The Chinese search terms are:???,?????,???,????,????,????,????,????,????.The corresponding English search terms are:injection,anthracyclines,Adriamycin,epirubicin,doxorubicin,pyrrobicin,roxithromycin,myocardial injury,cardiotoxicity,cardiac side effects.The retrieval time is from 2007 to now.According to the criteria of inclusion and exclusion,literatures were strictly screened and evaluated by Jadad scale.And literature data information were extracted and meta-analyzed by Revman 5.3.Bi-categorized variables were expressed by relative ratio(RR)and 95%confidence interval(CI),and publication bias was analyzed by funnel graph symmetry.Results:1.The results of analysis of the correlation between cardiotoxicity of anthracyclines and TCM syndromes(1)There is statistically significant between TCM syndrome types and molecular typing(P<0.05).There is no statistically significant among the difference in the distribution ratio of Her-2 overexpressed in the four TCM syndromes(P>0.05).Both LuminalA and LuminalB have the highest proportion of liver-qi stagnation syndrome and the lowest proportion of toxic heat accumulation,with statistically significant differences(P<0.05).There is no significant difference between qi and blood deficiency and liver and kidney Yin deficiency(P>0.05).Among trirple-negative breast cancer,the proportion of liver qi stagnation syndrome is the highest(P<0.05).There is no significant difference between the expression of ER and PR in TCM syndromes(P>0.05).There is significant difference between TCM syndrome type and the expression of Ki67(P<0.05).(2)Among the 152 patients,56 presented electrocardiogram abnormalities,with an incidence of 36.2%,of which ST-T change was the main change,and the incidence rate is 18.4%.The incidence of sinus bradycardia,sinus tachycardia,atrial premature contraction and ventricularpremature contraction are 6.6%,7.2%,2.6%and 2.0%,respectively.(3)Electrocardiogram abnormalities after the use of anthracyclines show statistically significant differences in age,menstrual status,previous history of hypertension,radiotherapy,and the cumulative dose of anthracyclines(P<0.05).There is no statistically significant difference in previous history of diabetes and BMI(P>0.05).(4)EF,CK and CKMB of the normal ECG group were compared with that of the abnormal group,and only CKMB is statistically significant(P<0.05).(5)The distribution of TCM syndromes in the ECG normal group and the abnormal group show that there is more qi and blood deficiency syndrome paitents in the abnormal,the difference is statistically significant(P<0.05).2.Meta-analysis of prevention and treatment of anthracycline cardiotoxicity by traditional Chinese medicine injection(1)The number of abnormal ECG in the observation group after chemotherapy is less than that in the control group and the difference is statistically significant[RR=0.44,95%CI(0.36,0.52),P<0.00001].(2)The decrease of LVEF in the observation group after chemotherapy is lower than that in the control group,and the difference is statistically significant[SMD=0.65,95%CI(0.40,0.90),P<0.00001].(3)The increase of cTnI in the observation group after chemotherapy is lower than that in the control group,and the difference is no significant[SMD=-0.12,95%CI(-0.25,0.02),P=0.09].(4)The increase of CKMB in the observation group after chemotherapy is lower than that in the control group,and the difference is statistically significant[SMD=-1.10,95%CI(-1.87,-0.32),P=0.005].Conclusion:1.There is a certain correlation between TCM syndrome type and molecular typing of breast cancer.In LuminalA type of breast cancer,liver qi stagnation syndrome is the most.Suggesting a good prognosis for breast cancer patients with liver qi stagnation syndrome.The TCM syndromes of breast cancer were independent of tumor size,clinical stage,ER,PR and HER2 expression.2.Age is a risk factor for cardiotoxicity induced by anthracyclines.3.Cardiotoxicity is likely to occur in patients with traditional Chinese medicine syndrome of deficiency of blood and qi.Patients with deficiency of blood and qi should be carefully treated with anthracycline chemotherapy drugs or applying cardiac protective drugs in advance.4.Injection replenishes qi and replenishes pulse,shenfu injection,shenmai injection,bufalin injection,astragalus injection,shenqi fuzheng injection,shengmai injection,compound radix sophorae,xinmailong injection,salvia miltiorrhiza injection has protection for anthracycline cardiac toxicity.Clinical application of anthracyclines chemotherapy drugs can be combined with the above traditional Chinese medicine injection.