Electrocardiogram Prediction Of Long-term Cardiovascular Adverse Events Induced By Radiation Therapy In Patients With Left Breast Cancer

Background and PurposeThe newly released global cancer statistics in 2021 show that breast cancer now outstrips lung cancer among female patients,ranking the top of global cancer incidence in 2020^[1].A variety of studies in recent years have shown that end-stage causes of death in breast cancer patients are mostly associated with cardiovascular diseases.Radiation therapy（RT）has greatly prolonged the survival time of many types of cancer,including breast cancer patients.During RT,the heart is inevitably exposed to a certain dose of radiation,which leads to different degrees of damage to the cardiovascular system and then the formation of radiation-induced heart disease（RIHD）.Due to the difference in RIHD induced by the same The same dose of RT in left breast cancer leads to much higher incidence of RIHD than that of right breast cancer;therefore,it is of great interest to find the new predictors and risk factors of RIHD in the left breast cancer patients.This research was conducted through the use of review the patients’records combined with a period of 18 months of follow-up study,after the left breast cancer patients received their first RT and the electrocardiogram changes were analyzed to predict long-term major adverse cardiovascular events（MACE）.MethodsFrom January 1,2005 to December 31,2010,patients diagnosed with left breast cancer in Harbin Medical University Cancer Hospital were enrolled in the study.The general information of the left side breast cancer patient and the detailed anti-tumor therapeutic methods,including age,smoking history,history the alcohol drinking,diabetes and hypertension,molecular subtypes,postoperative TNM stages（refer to the American joint committee on cancer published the eighth edition of the manual of tumor stage,based on the scope of the primary tumor,presence of regional lymph node metastasis,and distant metastasis of breast cancer staging including:stageⅠperiod,Ⅱperiod,Ⅲperiod andⅣperiod）,and mean cardiac radiation dose,chemotherapy course,targeted therapy,endocrine therapy,metastasis status were collected.According to the changes of electrocardiogram（ECG）18 months after the first RT application to left breast cancer patients,the patients were divided into abnormal ECG group and normal ECG group.The subjects were then followed up by telephone and compared the incident difference of long-term（within 10 years）MACE,all-cause mortality,and cardiovascular mortality between the two groups.The data were analyzed using logistics regression to determine the MACE risk factors;Kaplan-Meler survival was used to analyze if there is a correlation between occurrence of abnormal ECG and the survival and the incidence of long-term MACE in left breast cancer patients.ResultsThe basic clinical indices of left breast cancer patients with abnormal ECG and normal ECG were compared.Our data show that there was no significant difference in age,history of smoking,alcohol drinking,hypertension and diabetes mellitus,postoperative TNM stage and the metastasis status between the two groups（P>0.05）;however,there were significant differences in the course of chemotherapy and mean radiation dose to the heart,as well as molecular subtype of breast cancer and targeted therapy（P<0.05）.All subjects respectively had 25.4%MACE,43.9%all-cause mortality and 10.5%cardiovascular mortality in 10 years.Comparison of MACE incidence and all-cause mortality between the two groups,the incidence of MACE and all-cause mortality rate were significantly higher in the abnormal ECG group（39.0%vs.10.9%,P<0.01）and all-cause mortality（55.9%vs.30.9%,P<0.01）than in the normal ECG group.However,there was no significant difference in cardiovascular mortality between the two groups（10.2%vs.10.9%,P>0.05）.The data,generated from patients with MACE in 10 years,were analyzed using Non-conditional Logistics multivariate regression analysis.The results demonstrated that abnormal ECG,mean radiation dose to the heart,molecular subtypes of breast cancer（Luminal and HER 2 positive）were related factors for MACE.There was no significant correlation between the MACE patients’age,history of alcohol drinking,hypertension,molecular subtypes（triple negative type and HER 2 positive）（P>0.05）.Based on Kaplan-Meler survival analyses,we show that the occurrence of MACE is tightly associated with the ECG abnormality（P<0.05）;therefore,ECG abnormalities could be used as an independent predictor of long-term MACE in left breast cancer patients after RT.ConclusionsECG abnormalities after RT could be an independent predictor of long-term MACE in left breast cancer patients.The long-term cardiovascular risk,in patients with left breast cancer after RT,is affected by average radiation dose of the heart and molecular subtypes（Luminal and HER 2 positive）.The long-term cardiovascular risk,in patients with left breast cancer after RT,is associated with ECG abnormalities,average radiation dose of the heart and molecular subtypes（Luminal and HER 2positive）.The average radiation dose of the heart is positively correlated with the incidence of MACE,and patients with HER2 positive molecular subtypes are more likely to develop MACE than the patients with Luminal.