An Observational Study Of Cardiotoxicity In Breast Cancer Patients Using Herceptin Following Anthracycline

BackgroundAs many as 28%of patients arrest varying degrees of cardiotoxicity due to trastuzumab following anthracycline.As we all know,both trastuzumab and anthracycline drugs have cardiotoxicity.However,the sequential Herceptin-targeted therapy after anthracycline chemotherapy is still one of the most commonly used adjuvant therapy for HER-2-positive breast cancer in clinic practice.Whether sequential use of Herceptin-targeted therapy after anthracycline chemotherapy will further increase or superimpose the patient's cardiotoxicity is not yet clear.This article aims to prospectively observe the cardiotoxicity in the treatment of HER-2-positive breast cancer with the sequential anthracycline Herceptin regimen,then add clinical experience for cardiac safety when using anthracycline sequential Herceptin regimen during clinic practice.MethodsWe prospectively observed breast cancer patients who received chemotherapy in the chemotherapy department of Qilu Hospital Cancer Center of Shandong University from January 2016 to August 2017,including neoadjuvant chemotherapy,postoperative adjuvant chemotherapy,or palliative care.Inclusion criteria:1.Histopathological immunohistochemistry confirmed:Her-2 positive,regardless of hormone receptor ER,PR positive or not;2.Using target therapy with trastuzumab.At the baseline level,after the use of anthracycline drugs,after the use of trastuzumab the three nodes,enrolling all patients' echocardiography and peripheral venous blood sampling,and detected the following indicators:high-sensitivity cardiac troponin I(Hs-cTnI)and N-terminal B-type natriuretic peptide(NT-PROBNP).Record clinical information such as patient's age,BMI,hormone receptor status,anthracycline doses,and cumulative dose of anthracycline;record echocardiographic results(LVEF levels,E/e' levels);record experiments Room test results(high-sensitivity cardiac troponin I Hs-cTnI,N-terminal B-type natriuretic peptide NT-PROBNP)and statistical analysis.Statistical analysis was performed using IBM(?)SPSS(?)Statistics version 22,with a P value of<0.05 as statistically significant.The definition of cardiotoxicity is:Absolute drop of LVEF by 10%.ResultsA total of 46 HER-2 positive breast cancer patients were observed,4 of whom were interrupted.The remaining 42(100%)breast cancer patients received trastuzumab targeted therapy,of which 32(76%)patients received anthracycline chemotherapy before trastuzumab targeted therapy,10(24%)patients did not receive anthracycline chemotherapy before trastuzumab targeted therapy.Cumulative doses of epirubicin were 377.36± 136.61 mg/m2(mean±standard deviation).In all 42 analyzed patients,cardiotoxicity was observed in 7 patients(19%).All 7 patients were treated with anthracycline chemotherapy followed by sequential Herceptin-targeted therapy as adjuvant therapy.The first dose of trastuzumab was 8 mg/kg,followed by a therapeutic dose of 6 mg/kg.In all 42 analyzed patients,Baseline LVEF values were not statistically different in patients with or without cardiotoxicity(67%±4.5%vs.64%±3.6%;mean±standard deviation;P=0.056;(Table2).After use herceptin,LVEF values were statistically significant in patients with or without cardiotoxicity(67%± 4%vs.60%±7.3%,mean ±standard deviation;P = 0.001;(Table 2).In 7 patients with cardiotoxicity,cardiotoxicity was observed in only one case(14.3%)after anthracycline use(LVEF decrease>10%),while the remaining 6 cases(85.7%)were observed during sequential trastuzumab use following anthracycline use Cardiotoxicity(LVEF decrease>10%).There was no statistical difference of the LVEF values before and after treatment with Herceptin(66%±4.2%vs.60%± 7.3%;mean ± standard deviation;P = 0.114;(Table4).Hs-cTnI increased in all patients(Fig.1),it had a more significant increase in patients during the use of anthracyclines,but it had more significant increase in patients with cardiotoxicity(Fig.lb).Hs-cTnI tend to be stable in both cardiotoxicity or non-cardiotoxicity during Herceptin(Fig.1a;Fig.1a).Furthermore,the increment of hs-cTnl levels after anthracycline from baseline have a mild difference in patients with and without cardiotoxicity(6.78± 14.58vs.0.66± 4.56 ng/L;mean±standard deviation;P = 0.038;Table 2;Fig2).The difference between the increment of hs-cTnl levels after Herceptin from baseline and before Herceptin(after anthracycline)from baseline had no statistical significant(1.68±7.19 vs.-1.85±7.39 ng/L;mean±standard deviation;P=0.206;Table4;Fig3).Hs-cTnI increased in all patients(Fig.1),it had more significant increase in patients during the use of anthracyclines.During herceptin,he increase in cTnI levels was not significant(Figure 1).In 32 patients treated with anthracycline chemotherapy followed by Herceptin,the Hs-cTnl levels were significantly elevated during the use of anthracyclines,and there was no significant increase in Hs-cTnI levels during sequential Herceptin treatment,even observed a downward trend(Figure 2).In 7 patients with cardiotoxicity,Hs-cTnI levels increased significantly during the use of anthracyclines and there was a decreasing trend during sequential Herceptin(Fig.1b).Hs-cTnI levels increased during the use of anthracycline in 35 patients without cardiotoxicity,and a slight decrease was observed during Herceptin(Fig.1a).Baseline Hs-cTnI levels were not significantly different in patients with and without cardiotoxicity(5.30±3.97 vs.4.23±9.05 ng/L;mean±standard deviation;P = 0.76;Table 1).There was no significant difference in Hs-cTnI level and baseline Hs-cTnI level after anthracycline use(3.80±1.13 vs.5.47±1.68 ng/L;mean±standard deviation;P = 0.138).The difference between the Hs-cTnI level after anthracycline use and the baseline Hs-cTnl level(difference 1)was statistically different between the patients with or without cardiotoxicity(6.78±14.58 vs.0.66±4.56 ng/L;mean ± standard deviation;P = 0.038;Table 2;Fig.3).Difference between baseline Hs-cTnI and after use of anthracycline Hs-cTnI had no statistical significance(1.68±7.19 vs.-1.85±7.39 ng/L;mean±standard deviation;P = 0.206;Table 4;Figure 4).Independent sample T tests confirmed that baseline LVEF values were not statistically different in patients with or without cardiac toxicity(67%± 4.5%vs.64%± 3.6%;mean ± standard deviation;P = 0.056;Table 2).Multivariate regression analysis confirmed that there was no correlation between cardiotoxicity(yes or.no)and E/e' ratio increase above 15(yes or.no).There was no temporal relationship between the decrease in LVEF and the increase in E/e' ratio in 15 patients.Conclusion1.In HER-2-positive breast cancer anthracycline sequential Herceptin treatment,trastuzumab-targeted drugs do not further increase or add the patient's cardiotoxicity of anthracycline.2.The detection of Hs-cTnI can predict the early subclinical cardiac toxicity of anthracycline and trastuzumab in patients with breast cancer.The increment of Hs-cTnl level is more reliable than the Hs-cTnI level.3.LVEF has subsensitivity and hysteresis in suggesting subclinical cardiac injury due to anti-tumor therapy.