Trastuzumab-Induced Cardiomyopathy

doi:10.1016/j.cardfail.2008.02.002

Journal of Cardiac Failure

Volume 14, Issue 5, June 2008, Pages 437-444

https://doi.org/10.1016/j.cardfail.2008.02.002 Get rights and content

Abstract

Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

Section snippets

Pathogenesis

The exact mechanism of trastuzumab-induced cardiotoxicity is unknown. Fortunately, long-term experience with trastuzumab has shown that its cardiotoxicity is at least partially reversible. Determining the pathogenesis of toxicity is important because it may lead to cardioprotective drug therapies. Recently there has been an increased interest in discovering drugs that provide cardioprotection. Noma et al⁵ recently showed the cardioprotective effects against β-adrenergic stimulation via

Cardiovascular Surveillance Protocols

Since the significant level of cardiac side effects of trastuzumab became evident, screening for cardiac insufficiency became mandatory before initiating treatment with trastuzumab. Most studies screened patients before enrollment, both clinically and by an imaging modality for calculation of ejection fraction (EF). In most cases, either 2-dimensional echocardiography or multiple gated acquisition scan was considered acceptable, but in some instances only a single imaging modality was allowed

Future Directions

In summary, there are many questions regarding treatment with trastuzumab that remain unanswered. It is unclear whether the development of cardiotoxicity reverses only after discontinuation of trastuzumab, or if the addition of HF medications contribute to the restoration of normal cardiac function. If the latter is true, then which drugs are most efficacious, what is the optimal timing of drug administration, and whether there is a place for primary prevention of trastuzumab-induced

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Review ArticleTrastuzumab-Induced Cardiomyopathy

Abstract

Section snippets

Pathogenesis

Cardiovascular Surveillance Protocols

Future Directions

Semin Oncol

J Am Coll Cardiol

Clin Breast Cancer

Ann Oncol

Clin Breast Cancer

J Card Fail

Eur J Cancer

Lancet

Cardiac dysfunction in the trastuzumab clinical trials experience

J Clin Oncol

Clinical cardiac tolerability of trastuzumab

J Clin Oncol

Trastuzumab in the treatment of metastatic breast cancer: anticancer therapy versus cardiotoxicity

Circulation

Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection

J Clin Invest

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

Nat Rev Cancer

Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience

J Clin Oncol

Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment

J Clin Oncol

ErbB2 is essential in the prevention of dilated cardiomyopathy

Nat Med

Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy

Proc Natl Acad Sci U S A

Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity

Circulation

Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer

J Clin Oncol

Review Article
Trastuzumab-Induced Cardiomyopathy