How does Herceptin cause cardiotoxicity?

Cardiotoxicity of trastuzumab is considered to be the result of attenuated HER2-mediated signaling in the heart, culminating in decreased functionality of cardiac myocytes. HER2 appears to function as a compensatory mechanism acting against cardiac stress, such as anthracycline-induced cardiotoxicity.

How does Herceptin cause heart failure?

During Herceptin treatment, which is recommended for one year, toxicity can cause the heart to become too weak to pump blood. All patients on Herceptin undergo regular cardiac tests, such as an echocardiogram, to look for possible heart damage.

Does trastuzumab cause heart failure?

Symptomatic heart failure, a serious adverse effect of trastuzumab, occurs in 1% to 4% of patients treated with the antibody, whereas left ventricular ejection fraction declines substantially in 10% of patients. The prevalence of cardiotoxic effects of trastuzumab appears to increase with exposure to anthracyclines.

How is trastuzumab related to cardiotoxicity of the myocardium?

Pathogenesis. Trastuzumab cardiotoxicity may be induced by direct binding of trastuzumab to HER2 expressed on the myocardium, leading to an insufficient compensatory mechanism. Based on these data, it can be envisioned that trastuzumab-related cardiotoxicity, occurring after anthracyclines, is a two-step process.

What are the mechanisms of action of trastuzumab?

TRASTUZUMAB AND MECHANISMS OF ACTION Trastuzumab, a humanized monoclonal antibody directed against epidermal growth factor receptor 2 (HER2), has been approved to treat multiple oncologic conditions, including HER2-positive breast cancers in adjuvant, neoadjuvant, and metastatic settings and metastatic gastric cancer [1,2,3].

What are the mechanisms of cancer therapy induced cardiotoxicity?

Mechanisms of cancer therapy‐induced cardiotoxicity include a combination of on‐target effects on signaling cascades essential to both cancer progression and normal cardiac function and off‐target effects due to nonselective actions.

How are trastuzumab and anthracycline chemotherapy related?

The mechanism of trastuzumab-induced cardiac toxicity is still unclear; however, an association with anthracycline chemotherapy clearly exists. Figure 1 represents the HER2 signal transduction pathway and indicates the potential mechanism of action of trastuzumab.