Cardiotoxicity of Epidermal Growth Factor Receptor 2-Targeted Drugs for Breast Cancer

Abstract

Breast cancer is the most common form of cancer in women and its incidence has been increasing over the years. Human epidermal growth factor receptor 2 (HER2 or ErbB2) overexpression is responsible for 20 to 25% of invasive breast cancers, and is associated with poor prognosis. HER2-targeted therapy has significantly improved overall survival rates in patients with HER2-positive breast cancer. However, despite the benefits of this therapy, its cardiotoxicity is a major concern, especially when HER2-targeted therapy is used in conjunction with anthracyclines. At present, the mechanism of this cardiotoxicity is not fully understood. It is thought that HER2-targeting drugs inhibit HER2/NRG 1 dimer formation, causing an increase in ROS in the mitochondria of cardiomyocytes and inhibiting the PI3K/Akt and Ras/MAPK pathways, resulting in cell apoptosis. Antioxidants, ACE inhibitors, angiotensin II receptor blockers, β-blockers, statins and other drugs may have a cardioprotective effect when used with ErbB2-targeting drugs. NT-proBNP can be used to monitor trastuzumab-induced cardiotoxicity during HER2-targeted treatment and may serve as a biological marker for clinical prediction of cardiotoxicity. Measuring NT-proBNP is non-invasive, inexpensive and reproducible, therefore is worthy of the attention of clinicians. The aim of this review is to discuss the potential mechanisms, clinical features, diagnostic strategies, and intervention strategies related to cardiotoxicity of ErbB2-targeting drugs.

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

“…Baseline NP and cTn measurement are recommended in high-and very high-risk patients prior to anti-HER2-targeted therapies. 227,228 I C…”

Virus-like Particle (VLP) Vaccines for Cancer Immunotherapy

“…An ideal antigen should be exclusively expressed in cancer cells, not found in healthy cells, be vital for the survival of the cells, and stimulate a strong immune response [ 4 , 88 ]. While targeting highly expressed molecules is a potential approach, it is important to take into account the potential for autoimmune responses towards normal tissues that express these molecules at lower levels, such as HER-2 in cardiac cells [ 89 , 90 ].…”

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy

“…The patients were randomly randomized to receive either spironolactone or a placebo, both of which were given in conjunction with anthracycline-containing chemotherapy. During at least 24 weeks of treatment including 3 weeks after the conclusion of anthracycline-containing chemotherapy, spironolactone retained diastolic function, lowered the rise in TnI and NT-proBNP, and halted the loss of LVEF [94,95]. A schematic diagram is shown with the mechanism involved in relation to the cardiotoxicity caused by anthracyclines (Figure 7D).…”