Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction

Image by <a href=";utm_medium=referral&amp;utm_campaign=image&amp;utm_content=2658206">Peter Lomas</a> from <a href=";utm_medium=referral&amp;utm_campaign=image&amp;utm_content=2658206">Pixabay</a>
Submitted: December 8, 2021
Accepted: January 28, 2022
Published: February 17, 2022
Abstract Views: 1672
PDF: 425
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity:  two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.



PlumX Metrics


Download data is not yet available.


Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. DOI:
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016;37:2768-801. DOI:
Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail 2020;22:1945-60. DOI:
Čelutkienė J, Pudil R, López-Fernández T, et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC). Eur J Heart Fail 2020;22:1504-24. Erratum in: Eur J Heart Fail 2021;23:345. DOI:
Lancellotti P, Suter TM, Lopez-Fernandez T, et al. Cardio-Oncology Services: rationale, organization, and implementation: A report from the ESC Cardio-Oncology council. Eur Heart J 2019;40:1756-63. DOI:
Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol 2020;31:171-90. DOI:
Lu CY, Srasuebkul P, Drew AK, et al. Trastuzumab therapy in Australia: which patients with HER2+ metastatic breast cancer are assessed for cardiac function? Breast 2013;22:482-7. DOI:
Daniels B, Kiely BE, Lord SJ, et al. Trastuzumab for metastatic breast cancer: Real world outcomes from an Australian whole-of-population cohort (2001-2016). Breast 2018;38:7-13. DOI:
Dang CT, Blaes A, Lynce F, et al. Left ventricular ejection fraction monitoring adherence rates: Why so low? JACC Cardiovasc Imaging 2018;11:1094-7. DOI:
Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63. DOI:
Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1-39. DOI:
Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2014;15:1063-93. DOI:
Herrmann J, Lenihan D, Armenian S, et. al. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J 2022;43:280-99. DOI:
López-Sendón J, Álvarez-Ortega C, Zamora Auñon P, et al. Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry. Eur Heart J 2020;41:1720-9. DOI:
Pardo Sanz A, Zamorano JL. 'Cardiotoxicity': time to define new targets? Eur Heart J 2020;41:1730-2. DOI:
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891-975. DOI:
Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. J Clin Oncol 2006;24:4107-15. DOI:
Pistilli B, Marcellusi A, Latini L, et al. Cardiotoxicity related to long-term trastuzumab therapy in metastatic breast cancer: the potential role of treatment duration and cardiac risk factors. Breast J 2015;21:318-21. DOI:
Calvillo-Argüelles O, Abdel-Qadir H, Suntheralingam S, et al. Trastuzumab-related cardiotoxicity and cardiac care in patients with HER2 positive metastatic breast cancer. Am J Cardiol 2020;125:1270-5. DOI:
Blanter JB, Frishman WH. The preventive role of angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers and β-adrenergic blockers in anthracycline- and trastuzumab-induced cardiotoxicity. Cardiol Rev 2019;27:256-9. DOI:
Brown SA, Okwuosa TM, Barac A, Volgman AS. The role of angiotensin-converting enzyme inhibitors and β-blockers in primary prevention of cardiac dysfunction in breast cancer patients. J Am Heart Assoc 2020;9:e015327. DOI:
Sun Y, Li T, Zhang Y, Zhang Q. Evaluation of left ventricular ejection fractions in breast cancer patients undergoing long-term trastuzumab treatment. Med Sci Monit 2016;22:5035-40. DOI:
Huang P, Dai S, Ye Z, et al. Long-term tolerance and cardiac function in breast cancer patients receiving trastuzumab therapy. Oncotarget 2017;8:2069-75. DOI:
Bouwer NI, Steenbruggen TG, van Rosmalen J, et al. Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring? Breast Cancer Res Treat 2021;186:851-62 DOI:
Müller V, Clemens M, Jassem J, et al. Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer. BMC Cancer 2018;18:295. DOI:
Francesco Perone, Cardiology Department, La Paz University Hospital, IdiPAZ Research institute, Madrid

Cardiology Department, University of L'Aquila, Italy

How to Cite

Perone, Francesco, Pilar Zamora Auñon, Laura Rodríguez, David Vinal, Juan Caro-Codon, Ana Pertejo, Virginia Martínez Marín, Enrique Espinosa, and Teresa López-Fernández. 2022. “Cardiac Monitoring During Trastuzumab Therapy in Metastatic Breast Cancer: Early Incidence of Cardiac Dysfunction”. Monaldi Archives for Chest Disease 92 (4).