Trastuzumab-induced cardiotoxicity

Clinical and prognostic implications of troponin I evaluation

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Abstract

Purpose: Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods: In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results: TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P <.001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P <.001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P <.001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P <.001). Conclusion: TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

Original languageEnglish
Pages (from-to)3910-3916
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number25
DOIs
Publication statusPublished - Sep 1 2010

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Troponin I
Stroke Volume
Heart Failure
Cardiotoxicity
Trastuzumab
Therapeutics
Enalapril

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

@article{7cbae7b416bb498a948542f11b0dc2ab,
title = "Trastuzumab-induced cardiotoxicity: Clinical and prognostic implications of troponin I evaluation",
abstract = "Purpose: Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34{\%} of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods: In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50{\%}. Recovery from TIC was defined as LVEF increase above 50{\%}. Results: TIC occurred in 42 patients (17{\%}) and was more frequent in patients with TNI elevation (TNI+; 62{\%} v 5{\%}; P <.001). Twenty-five patients (60{\%}) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35{\%} v 100{\%}; P <.001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95{\%} CI, 11.6 to 45.5; P <.001) and of lack of LVEF recovery (HR, 2.88; 95{\%} CI,1.78 to 4.65; P <.001). Conclusion: TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.",
author = "Daniela Cardinale and Alessandro Colombo and Rosalba Torrisi and Sandri, {Maria T.} and Maurizio Civelli and Michela Salvatici and Giuseppina Lamantia and Nicola Colombo and Sarah Cortinovis and Dessanai, {Maria A.} and Franco Nol{\`e} and Fabrizio Veglia and Cipolla, {Carlo M.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1200/JCO.2009.27.3615",
language = "English",
volume = "28",
pages = "3910--3916",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "25",

}

TY - JOUR

T1 - Trastuzumab-induced cardiotoxicity

T2 - Clinical and prognostic implications of troponin I evaluation

AU - Cardinale, Daniela

AU - Colombo, Alessandro

AU - Torrisi, Rosalba

AU - Sandri, Maria T.

AU - Civelli, Maurizio

AU - Salvatici, Michela

AU - Lamantia, Giuseppina

AU - Colombo, Nicola

AU - Cortinovis, Sarah

AU - Dessanai, Maria A.

AU - Nolè, Franco

AU - Veglia, Fabrizio

AU - Cipolla, Carlo M.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Purpose: Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods: In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results: TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P <.001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P <.001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P <.001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P <.001). Conclusion: TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

AB - Purpose: Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods: In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results: TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P <.001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P <.001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P <.001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P <.001). Conclusion: TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

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U2 - 10.1200/JCO.2009.27.3615

DO - 10.1200/JCO.2009.27.3615

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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