Risk Analysis Of Cardiotoxicity Related To Therapy In Patients With Early Breast Cancer

Purpose:The main purpose of this study is to investigate the incidence of cardiotoxicity within four years of anti-tumor therapy among patients with early breast cancer,and evaluate potential risk factors in clinical practice.Methods:1.From January 2010 to January 2014,the patients who diagnosed with early invasive breast cancer were collected from the The First Hospital Affiliated to Dalian Medical University.All patients received neoadjuvant or adjuvant treatment and had complete clinical and pathological data.2.Exclusion criteria:patients previously diagnosed with breast cancer or other cancer who received anti-tumor therapy;patients previously diagnosed with heart failure or left ventricular dysfunction;patients diagnosed with multiple primary tumors and receiving anti-tumor therapy;breast cancer recurrence occured in patients and received the anti-tumor therapy.A total of 408 patients were eligible.Count the cases of cardiac toxicity complications and retrospectively analyze the incidence of cardiac toxicity within four years of anti-tumor therapy in patients with early breast cancer.3.Collected 408 cases of patients with the following informations:diagnosed age,body mass index(BMI),the tumor location,tumor stage,estrogen receptor(ER)status,progesterone receptor(PR)status,endocrine therapy,history of hypertension,history of coronary heart disease,history of diabetes,adjuvant treatment or neoadjuvant treatment,trastuzumab therapy,chemotherapy treatment,radiation therapy,the incidence of cardiac toxicity.Retrospectively analyze the correlation between the index and the occurrence of cardiac toxicity.4.Statistical Methods:All data were processed by SPSS 17.0 software.Use the chi-square test analyze the characteristics and distribution between the trastuzumab treatment group and the conventional chemotherapy group and calculate cumulative incidence of cardiac toxicity.The cumulative incidence of cardiac toxicity curves was drew by Kaplan-Meier test.The difference of cardiotoxicity incidence between the groups was analyzed by Log-Rank test.COX univariate analysis filtered the risk factors that may affect the cardiac toxicity,COX multivariate regression model selected the independent risk factors that may affect the cardiac toxicity.P values less than 0.05 was statistically different,less than 0.01 was statistically significant difference.Results:1.408 cases of patients,53 cases(13.0%)who performed with cardiac toxicity complications,14 cases of trastuzumab combined with chemotherapy group,39 cases of conventional chemotherapy group,among the two groups,the cumulative incidence of cardiac toxicity was 23.7%and 11.2%(respectively P<0.05)within four years,the cumulative incidence of cardiac toxicity when treated with trastuzumab combined with chemotherapy was higher than the conventional chemotherapy groups.2.According to trastuzumab therapy and anthracycline,the 408 cases were divided into two-drug group(trastuzumab combined with anthracycline)in 28 cases,monotherapy group(trastuzumab or anthracene ring drugs)326 cases,drug-free group(no Herceptin without anthracyclines)54 cases.The incidence of cardiac toxicity in two-drug group was 32.1%,12.3%in monotherapy group,7.4%in non-drug group.Fisher test results P values less than 0.05,trastuzumab combined with anthracycline therapy increases the incidence of cardiac toxicity,two drugs showed a additive effect.3.COX regression analysis among 408 cases of patients showed that taxanes and cyclophosphamide chemotherapy related with cardiac toxicity,but none of them truned into the independent risk factor.Trastuzumab treatment was proved to be an independent risk factor for the occurrence of cardiac toxicity(P<0.001),combinationed with chemotherapy the risk for cardiac toxicity complications(HR:5.041,95%CI:2.399-2.265)up to 5.041 times.History of coronary heart disease was a potential factor which increased the risk of cardiac toxicity(P<0.001,HR 6.812,95%Cl,3.503-13.247).Anthracyclines significantly affected the incidence of cardiac toxicity(P<0.001).Radiotherapy significantly increased the risk of cardiac toxicity(P<0.001,HR 2.890,95%CI,1.662-5.04),radiotherapy located on left and right chest wall was no significant difference(P=0.486).4.COX regression analysis of 59 cases who treated with trastuzumab combined chemotherapy group showed similar results to the overall population.Anthracycline therapy,history of coronary heart disease and radiotherapy were significantly associated with cardiac toxicity.The risk of patients who had a history of coronary heart disease appeared with cardiac toxicity complications was significantly increased(HR 16.242vs6.812),the risk of cardiac toxicity after radiotherapy also significantly increased(HR 9.513vs2.890),patients who had a history of coronary heart disease or received radiotherapy after trastuzumab combined chemotherapy treatment increased cardiac risk.5.Elderly(aged ≥60 years)was uncorrelated with cardiac toxicity(P=0.057),but among elderly patients the incidence of cardiac toxicity was higher(19.4%vs11.1%,P=0.038).Conclusion1.In this study,Independent cardiac toxicity risk factors for patients with early breast cancer received anti-tumor therapy were associated with trastuzumab targeted therapy,anthracycline treatment,history of coronary heart disease and radiation therapy.When treated with trastuzumab combined anthracycline chemotherapy the incidence of cardiotoxicity was highest,Trastuzumab combined anthracycline chemotherapy showed a additive effect.2.When treated with chemotherapy combined with trastuzumab targeted treatment,the cardiac toxicity risk for patients with history of coronary heart disease and previous radiation therapy was increased exponentially.3.Taxane and cyclophosphamide was associated with cardiac toxicity,but both of which were not the independent risk factor for cardiac toxicity.4.Elderly(aged≥60 years)was uncorrelated with cardiac toxicity,but among elderly patients the incidence of cardiac toxicity was higher.5.Radiotherapy significantly increased the risk of cardiac toxicity,radiotherapy located on left and right chest wall was no significant difference.