HER2-targeted therapies and cardiotoxicity: From major concern to manageable risk
Rio Putra Pamungkas1, Laras Pratiwi1, Henry Sutanto1
1Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
Abstract:
HER2-targeted therapies have dramatically improved outcomes for patients with HER2-positive breast cancer, but their potential for cardiotoxicity remains a critical clinical concern. Early trials reported high rates of cardiac dysfunction, particularly with concomitant anthracycline use, prompting the development of intensive cardiac monitoring strategies. However, emerging evidence suggests that most cardiotoxic events are asymptomatic, reversible, and rarely require permanent treatment discontinuation, particularly with newer agents such as antibody-drug conjugates. Clinical determinants include baseline left ventricular dysfunction, age, comorbidities, and combination chemotherapy, while biomarkers and advanced imaging are promising tools for early detection. Mechanistically, HER2 inhibition disrupts cardiomyocyte survival pathways and mitochondrial function, but the relationship between these changes and clinically meaningful heart failure remains incompletely defined. Recent studies, including SAFE-HEaRt, demonstrate that HER2 therapy can often be safely continued under cardio-oncology supervision with appropriate cardioprotective interventions. Nevertheless, gaps persist in risk stratification, long-term surveillance, and the integration of biomarkers and imaging into routine practice. This article critically examines the pathophysiology, clinical risk factors, and management of HER2 therapy-induced cardiotoxicity, ultimately arguing that with proper monitoring and multidisciplinary care, cardiotoxicity should not preclude optimal oncologic treatment.
Insights
HER2-targeted therapies improve breast cancer outcomes but can cause cardiotoxicity. However, most cardiac events are mild and reversible with monitoring, allowing safe continuation of HER2 treatment.
Area of Science:
- Cardio-oncology
- Medical oncology
- Cardiovascular medicine
Background:
- HER2-targeted therapies have revolutionized HER2-positive breast cancer treatment.
- Cardiotoxicity is a significant concern, historically linked to anthracyclines and HER2 inhibitors.
- Intensive cardiac monitoring was developed due to early concerns about cardiotoxicity.
Purpose of the Study:
- To critically examine the pathophysiology of HER2 therapy-induced cardiotoxicity.
- To review clinical risk factors and management strategies for cardiotoxicity.
- To argue for the safe continuation of HER2 therapy with monitoring and multidisciplinary care.
Main Methods:
- Review of early trial data and emerging evidence on HER2 therapy cardiotoxicity.
- Analysis of clinical determinants and potential biomarkers for cardiac dysfunction.
- Examination of mechanistic pathways of HER2 inhibition on cardiomyocyte function.
- Inclusion of findings from studies like SAFE-HEaRt on safe treatment continuation.
Main Results:
- Most cardiotoxic events are asymptomatic, reversible, and rarely require treatment cessation.
- Clinical determinants include baseline cardiac function, age, comorbidities, and chemotherapy combinations.
- Biomarkers and advanced imaging show promise for early detection of cardiac issues.
- HER2 therapy can often be safely managed with cardio-oncology supervision and cardioprotection.
Conclusions:
- Cardiotoxicity from HER2-targeted therapies is often manageable and reversible.
- Risk stratification, surveillance, and integrated care are crucial for optimal outcomes.
- With proper monitoring and multidisciplinary management, cardiotoxicity need not prevent effective HER2-targeted cancer treatment.
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