加减炙甘草汤对乳腺癌化疗致心脏毒性的临床观察及对心功能的保护作用分析

目的 探讨加减炙甘草汤对乳腺癌化疗所致的心脏毒性的临床观察及对心功能的保护作用.方法选择96例乳腺癌患者,通过随机数字表法分为对照组和观察组,每组48例.对照组患者接受多西他赛+多柔比星+环磷酰胺(TAC)化疗方案,观察组患者在此基础上联合加减炙甘草汤治疗,均以21 d为1个周期,连续治疗2个周期.比较两组患者治疗前后肌酸激酶(CK)、肌酸激酶同工酶MB(CK-MB)、心脏肌钙蛋白(cTnI)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)的变化,并比较心脏毒性的发生率.结果 治疗前,两组患者的CK、CK-MB、cTnI、LVEF、LVEDD、LVESD水平比较,差异均无统计学意义(P﹥0.05).治疗后,观察组患者的CK、CK-MB、cTnI、LVEF、LVEDD、LVESD水平与治疗前比较,差异均无统计学意义(P﹥0.05);对照组患者的CK、CK-MB、cTnI、LVEDD、LVESD水平均高于治疗前,LVEF水平低于治疗前,差异均有统计学意义(P﹤0.05);观察组患者的CK、CK-MB、cTnI、LVEDD、LVESD水平明显低于对照组,LVEF水平明显高于对照组,差异均有统计学意义(P﹤0.01);观察组患者的心脏毒性总发生率低于对照组(16.67% vs 37.50%),差异有统计学意义(P﹤0.05).结论 在乳腺癌患者的化疗过程中联合加减炙甘草汤治疗,效果显著,有助于缓解化疗所致的心脏毒性,保护心功能,临床应用价值高.     

血清cTnI联合BNP检测在乳腺癌化疗相关心脏毒性早期预测中的应用价值

目的:探究血清高敏心肌肌钙蛋白（cTnI）联合脑利钠肽（BNP）检测在乳腺癌化疗相关心脏毒性早期预测中的应用价值。方法:选择2015年12月至2016年12月本院收治的乳腺癌患者125例，所有患者均采用DA方案进行化疗，化疗前1天，每次化疗周期结束后第2天清晨采集静脉血液，收集血清，化学发光法检测血清cTnI、BNP水平，多普勒超声诊断仪对患者进行彩色多普勒超声检查，记录左室射血分数（LVEF），对所有患者进行随访，记录化疗过程中心脏毒性事件发生情况。结果:125例乳腺癌患者中有20例（16.00%）患者发生心脏毒性事件，心脏毒性患者中LVEF平均降低（15.38±1.23）%，8例患者出现明显的胸闷症状，心脏毒性与患者年龄、病理类型、淋巴结转移、绝经状态无关；无毒性组与心脏毒性组化疗前血清cTnI、BNP水平比较，差异无统计学意义（P＞0.05）。化疗后无毒性组与心脏毒性组患者血清cTnI、BNP水平均随着化疗周期的延长呈进行性升高，且同一周期下心脏毒性组血清cTnI、BNP水平显著高于无毒性组（P＜0.05）；ROC曲线图分析可知，6次化疗完成后血清cTnI、BNP水平诊断乳腺癌化疗相关心脏毒性的曲线下面积分别为0.943、0.887，诊断分界点分别为6.559 1×10-2 ng/mL、5×10-2 ng/mL，敏感性分别为90.00%、90.00%，特异性分别为84.76%、92.40%；血清cTnI、BNP联合检测对乳腺癌化疗相关心脏毒性诊断的曲线下面积为0.994，敏感性为94.60%，特异性为95.72%。结论:血清cTnI、BNP在乳腺癌化疗相关心脏毒性早期诊断中具有一定价值，且二者联合对乳腺癌化疗相关心脏毒性具有更高价值。     

乳腺癌患者术后化疗所致早期心脏毒性监测指标的研究

目的：观察乳腺癌术后辅助化疗患者的早期心脏毒性监测指标（左室射血分数、心肌做功指数、心电图以及心肌钙蛋白）的变化,评价其敏感性及临床意义。方法：选取42例乳腺癌患者,随机分为两组：干预组21例,患者接受TAC（多西紫杉醇＋吡喃阿霉素＋环磷酰胺）方案加右丙亚胺（右丙亚胺对吡喃阿霉素比值为10：1）;化疗组21例,常规接受TAC方案加安慰剂治疗。采用重复测量设计资料的方差分析化疗前、化疗后每周期以及化疗结束后3个月的心脏毒性指标变化情况。结果：两组患者不同周期左室射血分数（LVEF）变化无统计学意义（P〉0.05）;心肌做功（Tel）指数随着化疗周期的增加其测量结果存在统计学差异（P〈0.05）,且干预组患者Tel指数明显低于化疗组（P〈0.05）;两组患者心电图检查主要表现为一过性改变,均未出现明显特异性改变;在未达到吡喃阿霉素最大累积量前,血清中心肌钙蛋白（cTnI）与体内吡喃阿霉素累积量呈现零相关性（P〉0.05）。结论：蒽环类药物从第一次应用时对心脏就产生了明显的毒性,使用右丙亚胺对蒽环类药物所致心脏毒性有一定的防护作用。对两组患者心脏彩超、LVEF、心电图、cTnI等检查研究发现,上述指标对评价蒽环类药物所造成的亚临床左室结构与功能异常方面的敏感性与特异性较差,在临床上并不能及早有效评估化疗后患者早期心脏毒性,而Tel指数较之传统心脏超声、心电图、cTnI等能够更早、更敏感地评价蒽环类化疗药物对化疗患者心脏早期毒性。     

参麦注射液对接受表柔比星化疗的恶性肿瘤患者心肌酶水平的影响

心脏毒性是表柔比星应用过程中,发生率相对较高且较严重的一种毒副反应。为控制表柔比星的心脏毒性,从而使化疗顺利进行,本文将参麦注射液与含表柔比星方案联用,化疗后采用ELISA法检测患者血清肌酸激酶同工酶（CK—MB）、肌钙蛋白T（cTnT）水平,并以单用含表柔比星方案作为对照,以此评估参麦注射液对接受含表柔比星方案化疗的恶性肿瘤患者心脏毒性的影响。     

磷酸肌酸钠治疗原发性肝癌介入术后所致心肌损伤的疗效分析

目的：观察磷酸肌酸钠治疗原发性肝癌介入术后所致心肌损伤的临床疗效。方法：86例肝癌介入治疗术后的患者,随机分为对照组和观察组,对照组43例,观察组43例。两组给予常规的保护心肌药物,观察组在此基础上给予磷酸肌酸钠1g/ d 静注10天。观察治疗前后患者肌钙蛋白 I、CK - MB 和心电图改变情况。结果：两组治疗后肌钙蛋白 I、CK - MB 水平均下降,观察组下降较对照组明显（P ﹤0.05）。两组经过化疗共有73名患者出现心电图改变,治疗后两组心电图改变均有改善,观察组改善较明显（ P ﹤0.05）。结论：磷酸肌酸钠应用于肝癌介入治疗术后患者,对于预防和治疗化疗药物所致心脏毒性有较好的疗效。     

坎地沙坦联合小剂量卡维地洛或右丙亚胺对乳腺癌患者使用蒽环类化疗药物过程中的心脏保护作用对比研究

目的 对比研究坎地沙坦联合小剂量卡维地洛或右丙亚胺对乳腺癌患者使用蒽环类化疗药物过程中的心脏保护作用.方法 对104例乳腺癌患者的临床资料进行回顾性研究,按照不同治疗方式将患者分为试验组与对照组,每组52例.对照组患者在化疗方案中加用右丙亚胺;试验组患者在化疗方案中加用坎地沙坦联合小剂量卡维地洛.比较两组患者在治疗前以及治疗4、8个周期后心电图变化、肌钙蛋白水平、心肌重构指标以及不良反应发生情况.结果 化疗8个周期后,试验组患者QRS波群电压下降、心律失常、ST-T异常发生率明显低于对照组(P﹤0.01).化疗前两组患者LVEF、LVEDD及BNP比较,差异无统计学意义(P﹥0.05);化疗4、8个周期后,试验组患者LVEF下降程度低于对照组,LVEDD、BNP上升程度低于对照组(P﹤0.01).两组患者化疗4个周期后肌钙蛋白异常情况发生率比较,差异无统计学意义(P﹥0.05),化疗过程中两组患者未发生明显的肌钙蛋白异常情况(P﹥0.05).两组患者不良反应发生率比较,差异无统计学意义(P﹥0.05).结论 坎地沙坦联合小剂量卡维地洛能降低蒽环类化疗药物对癌症患者的心脏不良反应,且不良反应较轻,可在乳腺癌化疗患者中推广使用.     

右丙亚胺对女性乳腺癌患者术后化疗的心脏保护作用

[目的]观察右丙亚胺（DEX）对高复发风险早中期女性乳腺癌患者术后辅助化疗时的心脏保护作用。[方法]将患者随机分为治疗组和对照组,两组患者均采用EPI＋DTX为主的术后辅助化疗方案,治疗组同时加用DEX（DEX：EPI=10：1）,应用心肌肌钙蛋白T（cTnt）和左心室射血分数（LVEF）监测治疗前、第1周期、第3周期、治疗完成时、完成后半年、1年和2年的心脏功能状态,同时观察治疗的非心脏毒性。[结果]治疗组从第一周期开始cTnt明显上升,到治疗结束时达到最高,直到治疗后2年仍然维持在较高水平,而加用DEX组在治疗期间及治疗后水平都较低,两组LVEF在治疗各阶段无统计学差异．两组的非心脏副反应没有差异。[结论]EPI从第一次应用时对心脏就产生了明显的毒性,加用DEX可以降低这种心脏毒性。DEX＋EPI＋DTX方案适合具有高复发风险的女性乳腺癌的术后辅助化疗。     

右丙亚胺对乳腺癌患者在表柔比星化疗中的心脏保护作用

目的探讨右丙亚胺(Dexrazoxane,DEX)对乳腺癌患者在表柔比星(Epirubicin,EPI)化疗中的心脏保护作用。方法回顾性分析2012年7月至2015年1月徐州市中心医院行EPI辅助化疗的112例乳腺癌患者临床资料,依据有无联合应用DEX分为观察组(联合DEX)56例、对照组(不用DEX)56例。评价患者治疗前后心脏射血功能、肌钙蛋白T(cTnT)、心房钠尿肽(BNP)等血液毒性反应及化疗期间全身毒副反应的差异。结果观察组患者cTnT、BNP显著低于对照组,同时左室射血分数(LVEF)显著优于对照组(P0.05)。此外,化疗相关副反应组间比较差异无统计学意义(P0.05)。结论 DEX可显著降低EPI化疗期间心肌受损的程度,同时并不增加患者的全身毒副反应。     

经典型霍奇金淋巴瘤伴纵隔大肿块患者接受不同强度心脏保护方案化疗序贯放疗的心脏毒性分析

目的：探讨经典型霍奇金淋巴瘤（classical Hodgkin lymphomas, cHL）伴纵隔大肿块患者接受不同强度心脏保 护方案化疗序贯放疗后的心脏毒性的特点。方法：回顾性收集 2011 年 1 月至 2020 年 12 月我科收治的初治 cHL 伴纵隔大肿块患者共 150 例,患者均接受化疗序贯放疗治疗。根据不同强度的心脏保护方案分为表柔比星 + 博来霉素 + 长春新碱 + 达卡巴嗪方案组（EBVD 组）、EBVD 方案联合心脏保护剂右丙亚胺（dexrazoxane,D）组（EBVD+D 组）和多柔比星脂质体 + 博来霉素 + 长春新碱 + 达卡巴嗪方案组（PBVD 组）。收集分析整个治疗中以及治疗结束后 2 年的资料包括：患者基线特征、肌酸激酶同工酶 -MB（creatine kinase-MB isoenzyme,CK-MB）、B 型脑利钠肽（brain natriuretic peptide,BNP）、心肌肌钙蛋白 T/ 心肌肌钙蛋白 I（cardiac troponin T/I,cTnT/TnI）、心电图、超声心动图等检查结果以及心脏毒性相关的症状。统计同一期间我科收治的所有非纵隔大肿块 cHL 患者的心脏毒性发生率。结果：3 组之间的严重心脏毒性发生率从高到低依次为：EBVD 组（29.4%） > EBVD+D 组（18.9%） > PBVD 组（6.5%）,差异有统计学意义（P = 0.015）。初治cHL 伴纵隔大肿块患者心脏毒性发生率为 18.7%,不伴纵隔大肿块患者发生率为 5.6%。心脏毒性主要表现为胸闷、心悸、呼吸困难等症状（18%）,ST-T 改变或 T 波异常（42.7%）,QT 间期延长（16.7%）,窦性心动过速等心律失常（33.3%）, BNP 增高（13.3%）,左室射血分数（left ventricular ejection fraction,LVEF）下降（1.3%）,CK-MB（10.7%）、cTnT/TnI（6.0%）等生化指标增高。伴纵膈大肿块的 cHL 接受化疗序贯放疗治疗的心脏毒性更多地发生于年龄 > 50 岁、吸烟、肥胖、糖尿病以及接受高剂量纵隔放疗（≥ 36 Gy）的患者（P < 0.05）。结论：初治 cHL 伴纵隔大肿块患者较非纵隔大肿块患者更容易发生严重心脏毒性,高危因素包括年龄 > 50 岁、吸烟、肥胖、糖尿病以及接受高剂量纵隔放疗。采用新型蒽环类制剂替代传统蒽环类药物或加入心脏保护剂右丙亚胺可降低该类患者发生严重心脏毒性的几率。     

Q-T间期离散度联合肌钙蛋白I检测早期诊断乳腺癌蒽环类化疗所致心脏毒性的价值

目的:探讨Q-T间期离散度（QTd）联合肌钙蛋白I（cTnI）在蒽环类化疗药所致心脏毒性早期检测中的应用价值。方法:回顾性分析我医院2019年01月至2020年06月用蒽环类药物完成化疗的97例乳腺癌患者的临床资料。以左心射血分数（LVEF）下降幅度及充血性心衰症状为参考标准将纳入患者分为观察组（心脏毒性组）与对照组（非心脏毒性组）,统计其QTd、cTnI水平,用SPSS 25.0分析软件进行数据处理。结果:入组的97例患者中18人发生心脏毒性,发生率18.6%。化疗前对照组与观察组QTd、cTnI基线水平无明显统计学差异(P＞0.05);各化疗周期后QTd、cTnI水平均较基线水平明显升高（P＜0.05）;相同化疗周期观察组QTd、cTnI水平明显高于对照组（P＜0.05）。QTd、cTnI的ROC曲线下面积（AUC）分别为0.877、0.871,敏感性分别为85.4%、82.6%,特异性分别为96.5%、93.4%,联合应用时AUC为0.876,敏感性与特异性分别为84.0%、97.3%。结论:QTd、cTnI检测均可作为无创性评估蒽环类化疗药所致心脏毒性发生的前瞻性方法之一;QTd、cTnI联合应用具有更高的诊断价值。     

右丙亚胺用于乳腺癌术后化疗所致患者心肌损害的有效性和安全性

目的 探讨右丙亚胺对乳腺癌患者采用蒽环类化疗时心肌的保护作用.方法 选择乳腺癌术后接受CAF(环磷酰胺+阿霉素+5-氟尿嘧啶)方案和TE(多西他赛+表柔比星)方案化疗的患者98例.按照随机数字法将患者分为试验组和对照组各49例.对照组及实验组均采用CAF方案和TE方案化疗,试验组在给予阿霉素或表柔比星30 min前给予右丙亚胺(奥诺先)静脉滴注(右丙亚胺:阿霉素或表柔比星=10:1),30 min内滴完.结果 与治疗前比较,试验组治疗12个月以后出现血清BNP升高,对照组治疗6个月以后出现升高,差异有统计学意义(P<0.05);治疗6个月,12个月及24个月,试验组血清BNP低于对照组,差异有统计学意义(P<0.05).与治疗前比较,2组患者治疗6个月以后血清cTnT升高,差异有统计学意义(P<0.05);治疗6个月,12个月及24个月,试验组血清cTnT低于对照组,差异有统计学意义(P<0.05).试验组患者治疗后血清CK-MB与治疗前差异无统计学意义(P>0.05);对照组治疗12个月以后升高,差异有统计学意义(P<0.05).试验组治疗期间,LVEF与治疗前差异无统计学意义(P>0.05);对照组治疗6个月以后LVEF下降,差异有统计学意义(P<0.05);治疗6个月以后,对照组LVEF低于观察组,差异有统计学意义(P<0.05).2组患者不良反应发生情况差异无统计学意义(P>0.05).结论 右丙亚胺用于乳腺癌术后化疗可以明显减轻蒽环类药物的心脏毒性,保护心肌细胞,且不增加化疗的不良反应,提高患者化疗药物耐受性.     

Are Biomarkers Predictive of Anthracycline-Induced Cardiac Dysfunction?

Background: The early detection of anthracycline- induced cardiotoxicity is very important since it might be useful in prevention of cardiac decompensation. This study was designed with the intent of assessing the usefulness of cardiac troponin T (cTnT) and NT- Pro BNP estimation in early prediction of anthracycline induced cardiotoxicity. Materials and Methods: In this prospective study histologically proven breast cancer patients who were scheduled to receive anthracycline containing combination chemotherapy as a part of multimodality treatment were enrolled. Baseline cardiac evaluation was performed by echocardiography (ECHO) and biomarkers like cardiac troponin T (cTnT) and N terminal- pro brain natriuretic peptide (NT- Pro BNP). All patients underwent cTnT and NT- Pro BNP estimation within 24 hours of each cycle of chemotherapy and were followed up after 6 months of initiation of chemotherapy. Any changes in follow up ECHO were compared to ECHO at baseline and cTnT and NT- Pro BNP levels after each cycle of anthracycline-based chemotherapy. Results: Initial data were obtained for 33 patients. Mean change in left ventricular diastolic diameter (LVDD) within 6 months was 0.154 0 .433 cms (p value=0.049). Seven out of 33 patients had an increase in biomarker cTnT levels (p value=0.5). A significant change in baseline and follow up LVDD was observed in patients with raised cTnT levels (p value=0.026) whereas no change was seen in ejection fraction (EF) and left atrial diameters (LAD) within 6 months of chemotherapy. NT- Pro BNP levels increased in significant number of patients (p value 0.0001) but no statistically significant change was observed in the ECHO parameters within 6 months. Conclusions: Functional monitoring is a poorly effective method in early estimation of anthracycline induced cardiac dysfunction. Estimation of biomarkers after chemotherapy may allow stratification of patients in various risk groups, thereby opening window for interventional strategies in order to prevent permanent damage to the myocardium.     

二维与三维超声心动图斑点追踪技术检测乳腺癌蒽环类药物心脏毒性的可行性研究

目的:探讨二维与三维斑点追踪技术以及实时三维超声心动图在早期检测蒽环类药物所致心脏毒性中的价值,并评估其可行性.方法:对乳腺癌患者于蒽环类药物化疗前、化疗第3周期及化疗结束后行超声心动图检查,以3D LVEF结果为评价标准,统计分析各参数在评估心脏毒性中的临床价值.结果:共92例乳腺癌患者纳入研究.常规超声心动图以及2...     

右丙亚胺联合参麦注射液降低蒽环类药物心脏毒性的临床研究

  目的  比较右丙亚胺单用、参麦注射液单用, 或者联合使用参麦注射液和右丙亚胺对血液系统肿瘤患者蒽环类药物多疗程化疗所致心脏不良反应的临床意义, 进一步探讨降低蒽环类药物心脏毒性的途径。  方法  本研究入组120例血液系统肿瘤患者, 共分为4组, 每组30例。A组为参麦组, 在化疗基础上单用参麦注射液, 50 mL/d连用lw; B组为联合使用参麦注射液和右丙亚胺, 在应用蒽环类药物化疗前30 min快速静脉滴入右丙亚胺及阿霉素（剂量10:1）, 非阿霉素蒽环类药物折合成阿霉素。且在化疗开始之日起, 予以参麦注射液50 mL/d, 连用1w;C组为右丙亚胺组, 应用蒽环类药物化疗前30 min予右丙亚胺及阿霉素快速静脉滴入; A、B、C 3组为实验组, D组为空白对照组, 予以常规化疗; 4组患者均按要求完成2个化疗周期, 观察化疗前后4组患者的心电图改变以及超声心动图（左室射血分数LVEF）, B型利钠肽（BNP）, 肌钙蛋白I（TnI）的数值变化。  结果  通过比较化疗前后4组患者的心电图变化和左室射血分数（LVEF）、肌钙蛋白I（TnI）、B型利钠肽（BNP）的数值变化, 实验组心电图异常的发生率、LVEF下降百分比、TnI和BNP的数值升高均小于空白对照组（P < 0.05）。  结论  右丙亚胺、参麦注射液单用以及二者合用, 降低血液系统恶性肿瘤患者接受蒽环类药物多疗程化疗所致心脏毒性, 均有一定疗效, 其中右丙亚胺及参麦注射液联合疗效最佳, 而右丙亚胺单用对心肌细胞保护作用好于参麦注射液单用。在蒽环类药物化疗同时配伍使用参麦注射液及右丙亚胺, 可减低心脏毒性, 值得临床推广应用。      

The Role of Lisinopril and Bisoprolol to Prevent Anthracycline Induced Cardiotoxicity in Locally Advanced Breast Cancer Patients

Background: Anthracyclines are a class of chemotherapeutic agents that are used to treat many different cancers, including breast cancer. Although anthracyclines remain an effective and commonly used therapy, their use is limited by cardiotoxicity. Heart failure and left ventricular (LV) dysfunction are the short and long-term complications of anthracyline exposure occurring in 5% to 23% of patients. Recent prospective studies have investigated the prophylactic role of ACE inhibitors and beta-blockers as cardioprotective agents. This study aimed to evaluate whether the addition of lisinopril and bisoprolol could prevent anthracycline induced cardiotoxicity. Methods: In this randomized, controlled trial, 74 subjects with locally advanced breast cancer were randomly assigned to a group receiving lisinopril and bisoprolol (n=37) or to a control group (n=37). Lisinopril and bisoprolol was started simultaneously 24 h before the first cycle of chemotherapy. The initial dose was 2.5 mg each, once daily, and was increased gradually under close supervision to 10 mg if SBP persistently remained >90 mmHg and HR >60 bpm. Echocardiographic studies were performed before and after the 6th cycle of neoadjuvant anthracycline-based chemotherapy (FAC). The primary endpoint was the change from baseline LVEF. Results: There was no difference in baseline LVEF between intervention and control group (65.77 ± 4.56 % v 65.64 ± 455 %, p = 0.92). There was also no difference in total anthracycline doses between 2 groups (579.48 ± 65.10 mg vs 557.50 ± 47.76 mg, p = 0.18). However, after 6 cycles of FAC, the rate of decline in LVEF was greater in control group (-5.52 ± 8,90 %) than in the intervention group (-0.27 ± 5.73 %) with p = 0.017. No severe adverse effects occurred in the intervention group related to the treatment with lisinopril and bisoprolol. Conclusion: Combined treatment with lisinopril and bisoprolol may prevent anthracycline-induced cardiotoxicity in patients with locally advanced breast cancer treated with anthracycline-based chemotherapy. The clinical relevance of this study should be confirmed in larger studies with longer follow up time.     

High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: a pilot study

Monitoring of left ventricular ejection fraction (LVEF) is the current standard for detection of trastuzumab-induced cardiotoxicity; however, time-to-diagnosis and cost of assessment are suboptimal in women with early-stage breast cancer. We assessed the utility of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin I (cTnI) as serum biomarkers for early detection of trastuzumab-induced cardiotoxicity. Fifty-four women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were prospectively enrolled, and the relationship between elevated serum BNP, hs-CRP, and cTnI levels and clinically significant decreases in LVEF was examined. LVEF was monitored at 3-4 month intervals during trastuzumab treatment. Laboratory testing for candidate biomarkers was repeated every 3 weeks with each cycle of trastuzumab. Trastuzumab-induced cardiotoxicity was defined as a decrease in LVEF of ≥15% or to a value below 50%. A clinically significant decrease in LVEF was observed in 28.6% of women. Abnormal hs-CRP (≥3 mg/L) predicted decreased LVEF with a sensitivity of 92.9% (95% CI 66.1-99.8) and specificity of 45.7% (95% CI 28.8-63.4), and subjects with normal hs-CRP levels (<3 mg/L) have 94.1% negative predictive 94.1% (95% CI 70.3-99.9) suggesting that normal hs-CRP levels may be associated with low future risk for decreased LVEF; however, no association with BNP or cTnI was observed. A false positive would have a relatively low associated cost in breast cancer patients undergoing adjuvant trastuzumab therapy and would indicate continuation of routine observation during treatment through traditional means. The maximum hs-CRP value was observed a median of 78 days prior to detection of cardiotoxicity by decreased LVEF, and those with normal levels were at lower risk for cardiotoxicity. Regular monitoring of hs-CRP holds promise as a biomarker for identifying women with early-stage breast cancer at low risk for asymptomatic trastuzumab-induced cardiotoxicity. To our knowledge, this is the first study documenting the utility of a less expensive, reproducible, easily obtainable biomarker with rapid results for evaluating cardiotoxicity related to trastuzumab therapy.     

Evaluation of cardiac safety of lapatinib therapy for ErbB2-positive metastatic breast cancer: A single center experience

Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10?% of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250?mg per day continuously plus capecitabine at a dose of 2,000?mg/m² in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9?weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3?C60) weeks. The median age was 48 (range 28?C83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2?%) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8?%) had T wave negativity, 1 (3.8?%) had sinus tachycardia, 1 (3.8?%) had grade 1 (453?ms) QT prolongation, and 2 (7.7?%) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7?%) had increased BNP, 1 (3.8?%) had increased CK, and 1 (3.8?%) had increased CK?CMB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK?CMB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.     

Personalized Decision Making in Early Stage Breast Cancer: Applying Clinical Prediction Models for Anthracycline Cardiotoxicity and Breast Cancer Mortality Demonstrates Substantial Heterogeneity of Benefit-Harm Trade-off

BackgroundAnthracycline agents can cause cardiotoxicity. We used multivariable risk prediction models to identify a subset of patients with breast cancer at high risk of cardiotoxicity, for whom the harms of anthracycline chemotherapy may balance or exceed the benefits.Patients and MethodsA clinical prediction model for anthracycline cardiotoxicity was created in 967 patients with human epidermal growth factor receptor-negative breast cancer treated with doxorubicin in the ECOG-ACRIN study E5103. Cardiotoxicity was defined as left ventricular ejection fraction (LVEF) decline of ≥ 10% to < 50% and/or a centrally adjudicated clinical heart failure diagnosis. Patient-specific incremental absolute benefit of anthracyclines (compared with non-anthracycline taxane chemotherapy) was estimated using the PREDICT model to assess breast cancer mortality risk.ResultsOf the 967 women who initiated therapy, 51 (5.3%) developed cardiotoxicity (12 with clinical heart failure). In a multivariate model, increasing age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08), higher body mass index (OR, 1.06; 95% CI, 1.02-1.10), and lower baseline LVEF (OR, 0.93; 95% CI, 0.89-0.98) at baseline were significantly associated with cardiotoxicity. The concordance statistic of the risk model was 0.70 (95% CI, 0.63-0.77). In patients with low anticipated treatment benefit (n = 176) from the addition of anthracycline (< 2% absolute risk difference of breast cancer mortality at 10 years), 16 (9%) of 176 had a > 10% risk of cardiotoxicity and 61 (35%) of 176 had a 5% to 10% risk of cardiotoxicity at 1 year.ConclusionOlder age, higher body mass index, and lower baseline LVEF were associated with increased risk of cardiotoxicity. We identified a subgroup with low predicted absolute benefit of anthracyclines but with high predicted risk of cardiotoxicity. Additional studies are needed incorporating long-term cardiac outcomes and cardiotoxicity model external validation prior to implementation in routine clinical practice.