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Published in: Medical Oncology 12/2017

01-12-2017 | Original Paper

Factors for time to trastuzumab-induced cardiotoxicity in breast cancer patients

Authors: Mi Hyung Lee, Jeong Yee, Young Ju Kim, Jin Young Moon, Joo Hee Kim, Sandy Jeong Rhie, Hye Sun Gwak

Published in: Medical Oncology | Issue 12/2017

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Abstract

Trastuzumab is a drug used for the treatment of metastatic breast cancer patients. Due to blockage of the human epidermal growth factor receptor 2 signaling in cardiac myocytes, cardiotoxicity has been observed. There are many studies that investigated risk factors for trastuzumab-induced cardiotoxicity, but no study has been published for factors on the time to cardiotoxicity. This study aimed to investigate the factors for the time to occur trastuzumab-induced cardiotoxicity. From January 2014 to December 2015, a retrospective study was performed with breast cancer patients who were treated with trastuzumab. Associations between presence of and time to cardiotoxicity and various factors were analyzed. Based on multivariate models, it was found that baseline left ventricular ejection fraction (LVEF) < 62.5% (AHR 5.96, 95% CI 2543–13.95) and anthracycline-based chemotherapy (AHR 7.90, 95% CI 1.05–59.71) were significant factors for time to cardiotoxicity after adjusting other confounding factors. Multivariate analysis also showed that BMI ≥ 23 kg/m2 and baseline LVEF value < 62.5% increased cardiotoxicity 3.0 and 6.6 times, respectively. Our study showed that BMI ≥ 23 kg/m2, LVEF < 62.5%, and anthracycline-based chemotherapy were associated with time to trastuzumab-induced cardiotoxicity. Thus, close monitoring of cardiac function is recommended especially for patients using the above risk factors.
Literature
1.
go back to reference Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.CrossRefPubMed Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.CrossRefPubMed
2.
go back to reference Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogened. Science. 1987;235:177–82.CrossRefPubMed Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogened. Science. 1987;235:177–82.CrossRefPubMed
3.
go back to reference Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.CrossRefPubMed Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.CrossRefPubMed
4.
go back to reference Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol. 2007;18:977–84.CrossRefPubMed Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol. 2007;18:977–84.CrossRefPubMed
5.
go back to reference Seidman A, Hudis C, Pierri MK. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21.CrossRefPubMed Seidman A, Hudis C, Pierri MK. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21.CrossRefPubMed
6.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.CrossRefPubMed Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.CrossRefPubMed
7.
go back to reference Onitilo AA, Engel JM, Stankowski RV. Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf. 2014;5:154–66.CrossRefPubMedPubMedCentral Onitilo AA, Engel JM, Stankowski RV. Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf. 2014;5:154–66.CrossRefPubMedPubMedCentral
8.
go back to reference Belkacémi Y, Gligorov J, Ozsahin M, et al. Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. Ann Oncol. 2008;19:1110–6.CrossRefPubMed Belkacémi Y, Gligorov J, Ozsahin M, et al. Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. Ann Oncol. 2008;19:1110–6.CrossRefPubMed
9.
go back to reference Guenancia C, Lefebvre A, Cardinale D, et al. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2016;34:3157–65.CrossRefPubMedPubMedCentral Guenancia C, Lefebvre A, Cardinale D, et al. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J Clin Oncol. 2016;34:3157–65.CrossRefPubMedPubMedCentral
10.
11.
go back to reference Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389:1195–205.CrossRefPubMed Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389:1195–205.CrossRefPubMed
12.
go back to reference Guglin M, Hartlage G, Reynolds C, et al. Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study. J Card Fail. 2009;15:651–7.CrossRefPubMed Guglin M, Hartlage G, Reynolds C, et al. Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study. J Card Fail. 2009;15:651–7.CrossRefPubMed
13.
14.
go back to reference Pan WH, Yeh WT. How to define obesity? Evidence-based multiple action points for public awareness, screening, and treatment: an extension of Asian-Pacific recommendations. Asia Pac J Clin Nutr. 2008;17:370–4.PubMed Pan WH, Yeh WT. How to define obesity? Evidence-based multiple action points for public awareness, screening, and treatment: an extension of Asian-Pacific recommendations. Asia Pac J Clin Nutr. 2008;17:370–4.PubMed
15.
go back to reference Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–13.CrossRefPubMed Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–13.CrossRefPubMed
16.
go back to reference Tangiisuran B, Scutt G, Stevenson J, et al. Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model. PLoS ONE. 2014;9:e111254.CrossRefPubMedPubMedCentral Tangiisuran B, Scutt G, Stevenson J, et al. Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model. PLoS ONE. 2014;9:e111254.CrossRefPubMedPubMedCentral
17.
go back to reference Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23:2900–2.CrossRefPubMed Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23:2900–2.CrossRefPubMed
18.
go back to reference Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.CrossRefPubMed Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.CrossRefPubMed
19.
go back to reference Gordon LI, Burke MA, Singh AT, et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J Biol Chem. 2009;284:2080–7.CrossRefPubMedPubMedCentral Gordon LI, Burke MA, Singh AT, et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J Biol Chem. 2009;284:2080–7.CrossRefPubMedPubMedCentral
20.
go back to reference Farolfi A, Melegari E, Aquilina M, et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors. Heart. 2013;99:634–9.CrossRefPubMed Farolfi A, Melegari E, Aquilina M, et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors. Heart. 2013;99:634–9.CrossRefPubMed
21.
go back to reference Zeglinski M, Ludke A, Jassal DS, et al. Trastuzumab-induced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol. 2011;16:70–4.PubMedPubMedCentral Zeglinski M, Ludke A, Jassal DS, et al. Trastuzumab-induced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol. 2011;16:70–4.PubMedPubMedCentral
Metadata
Title
Factors for time to trastuzumab-induced cardiotoxicity in breast cancer patients
Authors
Mi Hyung Lee
Jeong Yee
Young Ju Kim
Jin Young Moon
Joo Hee Kim
Sandy Jeong Rhie
Hye Sun Gwak
Publication date
01-12-2017
Publisher
Springer US
Published in
Medical Oncology / Issue 12/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-017-1041-z

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