Cardiotoxicity Of Anti-HER-2 Monoclonal Antibodies In Patients With Breast Cancer

Objective(s):For patients with HER-2 positive breast cancer,comparing the the cardiotoxicity of anthracyclines chemotherapy followed by anti-HER-2monoclonal antibodies(trastuzumab,pertuzumab)targeted therapy with anthracycline chemotherapy.By retrospective analysis of the incidence,time of occurrence,and abnormalities of cardiac monitoring indicators,to provided a reference for the prediction and prevention of anti-HER-2 monoclonal antibody-related cardiotoxicity.Methods:In this study,datas of patients with HER-2 positive breast cancer who met the inclusion and exclusion criteria in our hospital since January 2018 to December 2022 were collected.According to different treatment regimens,the patients were divided into three groups: patients in group A(control group)were treated with anthracycline-based chemotherapy(EC-T regimen),52 cases;patients in group B were treated with anthracycline followed by trastuzumab(EC-TH regimen),50 cases;patients in group C were treated with anthracycline followed by trastuzumab combined with pertuzumab(EC-THP regimen),57 cases.Echocardiography was reviewed every three months for two years from beginning of treatment and cardiotoxicity was determined by meeting anyone of the following criteria:(1)Cardiomyopathy with reduced LVEF,decreased overall cardiac function,or significantly weakened interventricular septal motion;(2)Symptoms related to congestive heart failure;(3)Signs related to congestive heart failure such as third heart sound gallop,tachycardia,etc.;(4)With signs and symptoms of heart failure and a reduction in LVEF of at least 5% from baseline to an absolute value of <55%,or without symptoms and signs of heart failure but a reduction in LVEF of at least 10%to an absolute value of <55%.Collecting and comparing the baseline data,the incidence and time of cardiotoxicity among the three groups.The impact of anti-HER-2 monoclonal antibodies on the risk of cardiotoxicity was analyzed.Meanwhile,patients in groups B and C who used anti-HER-2 monoclonal antibody were monitored for Troponin I,N-terminal prohormone of brain natriuretic peptide,and ECG before each course of targeted therapy and in the early morning of the next day after treatment.By comparing the abnormal occurrence of monitoring indicators,the monitoring method with predictive value for the occurrence of cardiotoxicity in the process of targeted therapy with anti-HER-2 positive monoclonal antibodies was proposed.Results:(1)Incidence of cardiotoxicity:The baseline data of the three groups of patients,including general data such as age,height,weight,body mass index,hemoglobin concentration,and medical history data such as hypertension,diabetes,hyperlipidemia,family history of cardiovascular disease,did not show significant differences(P>0.05).Therefore,the incidence of cardiotoxicity in the three groups was comparable.The incidences of cardiotoxicity in group A,group B,and group C were respectively 7.69%,6.00%,and 8.77%,and there was no significant difference among them(P>0.05).(2)Occurrence time of cardiotoxicity:Comparing the patients with cardiotoxicity in group A,group B,and group C.The time when cardiotoxicity was first discovered in group A all occurred within 9 months after the administration of anthracyclines,early cardiotoxicity accounted for 75%.The time when cardiotoxicity was first discovered in group B and group C both occurred within 9 months after the administration of anti-HER-2 monoclonal antibodies,early cardiotoxicity accounted for 66.67%,80.00%.That is,the occurrence of cardiotoxicity in the three groups was mainly early cardiotoxicity.(3)Comparing the pre-treatment results and posttreatment results of Troponin I,N-terminal prohormone of brain natriuretic peptide,and Electrocardiogram during the using procedure with anti-HER-2 monoclonal antibodies in 107 patients in group B and group C.It was found that the numbers and abnormalities of abnormal Troponin I,N-terminal prohormone of brain natriuretic peptide,and ECG were 6cases(5.61%),13cases(12.15%)and 38cases(35.51%),respectively.The incidence of abnormal Troponin I abnormalities increased significantly(P<0.05)and the incidences of abnormal N-terminal prohormone of brain natriuretic peptide and ECG increased highly significantly(P<0.01)after the treament of anti-HER-2 monoclonal antibodies.At the same time,comparing the incidence of abnormal cardiac monitoring indicators between cardiotoxic patients and non-cardiotoxic patients,it was found that the incidences of abnormal Troponin I,N-terminal prohormone of brain natriuretic peptide and ECG in cardiotoxic patients was significantly higher than that of non-cardiotoxic patients(P<0.01).Conclusion(s):(1)In the absence of significant differences in baseline data,whether it was trastuzumab single-target therapy or trastuzumab combined with pertuzumab dual-target therapy after the use of anthracyclines,did not significantly increase the risk of cardiotoxicity based on anthracyclines.In addition,the trastuzumab combined with pertuzumab dual-target therapy also did not significantly increase the risk of cardiotoxicity compared with trastuzumab single-target therapy.(2)During the first year of treatment with anthracyclines and anti-HER-2monoclonal antibodies,patient should be monitored regularly for cardiac function,and corresponding treatment should be given at an appropriate time combined with specialist consultation opinions.(3)The abnormal changes of Troponin I,N-terminal prohormone of brain natriuretic peptide,Electrocardiograph have early warning value for the occurrence of anti-HER-2 monoclonal antibody-related cardiotoxicity and subclinical cardiotoxicity during the treatment,and the three monitoring indicators are feasible and reproducible in clinical practice.