Mokuyasu Seiichi, Suzuki Yasuhiro, Kawahara Ei, Seto Takayuki, Tokuda Yutaka
Department of Clinical Laboratory, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Graduate School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Breast Cancer. 2015 Nov;22(6):563-9. doi: 10.1007/s12282-014-0520-8. Epub 2014 Feb 23.
Breast cancer treatment with trastuzumab, a monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), has largely been successful in improving the prognosis of HER2-positive disease. However, a critical issue associated with trastuzumab treatment is its cardiotoxic adverse effects, including cardiac insufficiency.
We measured levels of cardiac troponin I, a marker of myocardial damage, with a highly sensitive method (hs-cTnI) using a fully automated chemiluminescent immunoassay system (ADVIA Centaur(®) XP) in breast cancer patients and examined the relationship between administration of trastuzumab and epirubicin and concentrations of hs-cTnI.
The coefficient of variation for within-run repeatability was 1.34-5.93 %, using plasma pools and controls of 3 concentrations, and that for between-run reproducibility was 3.99-8.79 %, indicating high precision of the assay. In a dilutional linearity test with highly concentrated specimens, hs-cTnI values could be measured up to 50 ng/mL with linearity. No influence from coexisting substances was observed. The concentration of hs-cTnI was at or above the reference range (0.04 ng/mL) in 9 of 214 total breast cancer cases (4.2 %). The hs-cTnI concentration was at or above the reference range in 4 of 49 cases (8.2 %) that were administered trastuzumab, and in 5 of 165 cases (3.0 %) that were not. Trastuzumab did not cause elevation of hs-cTnI when not administered in combination with epirubicin.
These results suggest that epirubicin and trastuzumab cause cardiotoxicity through different mechanisms. Epirubicin can cause myocardial necrosis, while trastuzumab can cause cardiomyopathy without myocardial necrosis.
曲妥珠单抗是一种靶向人表皮生长因子受体2（HER2）的单克隆抗体，用其治疗乳腺癌在很大程度上成功改善了HER2阳性疾病的预后。然而，与曲妥珠单抗治疗相关的一个关键问题是其心脏毒性不良反应，包括心脏功能不全。
我们使用全自动化学发光免疫分析系统（ADVIA Centaur® XP），通过一种高灵敏度方法（hs-cTnI）测定乳腺癌患者心肌损伤标志物心肌肌钙蛋白I的水平，并研究曲妥珠单抗和表柔比星的给药与hs-cTnI浓度之间的关系。
使用3种浓度的血浆池和对照进行批内重复性检测时，变异系数为1.34 - 5.93%，批间再现性检测时变异系数为3.99 - 8.79%，表明该检测具有高精度。在对高浓度标本进行的稀释线性试验中，hs-cTnI值在高达50 ng/mL时均可线性测量。未观察到共存物质的影响。在214例乳腺癌患者中，有9例（4.2%）的hs-cTnI浓度处于或高于参考范围（0.04 ng/mL）。在接受曲妥珠单抗治疗的49例患者中，有4例（8.2%）的hs-cTnI浓度处于或高于参考范围，而在未接受曲妥珠单抗治疗的165例患者中有5例（3.0%）如此。当曲妥珠单抗不与表柔比星联合使用时，不会导致hs-cTnI升高。
这些结果表明，表柔比星和曲妥珠单抗通过不同机制导致心脏毒性。表柔比星可引起心肌坏死，而曲妥珠单抗可导致无心肌坏死的心肌病。
