title: High-sensitivity cardiac troponin I detection for 2 types of drug-induced cardiotoxicity in patients with breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Laboratory, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. mokuyasu@is.icc.u-tokai.ac.jp.|Graduate School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan. mokuyasu@is.icc.u-tokai.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mokuyasu
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Graduate School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Ei
authors.initials: E
authors.lastname: Kawahara
authors.affiliation: Department of Clinical Laboratory, Tokai University OISO Hospital, 21-1 Gakkyo, Oiso, Naka, Kanagawa, 259-0198, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D066126:Cardiotoxicity / Q000097:blood* / Q000209:etiology; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008163:Luminescent Measurements / Q000379:methods; D008875:Middle Aged; D012016:Reference Values; D012680:Sensitivity and Specificity; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I; D015251:Epirubicin; D000068878:Trastuzumab
keywords: Cardiotoxicity; Epirubicin; High-sensitivity cardiac troponin I; Trastuzumab