Perspective:

Trastuzumab is a monoclonal antibody that targets human epidermal growth factor receptor-2 (HER-2) positive breast cancer cells. Approximately 20-30% of breast cancer patients overexpress HER-2/ErbB2 receptors and experience more aggressive tumors with lower survival rates. Treatment with trastuzumab significantly impacts time to progression and clinical survival, and is currently approved as first-line therapy for HER-2 positive metastatic breast cancer. HER receptors are involved in embryonic development and repair mechanisms of the heart, which when altered, may cause cardiac dysfunction. Trastuzumab generally presents with an asymptomatic decline in LV function, with some progressing to overt CHF. It is still unknown whether asymptomatic decline in LVEF in breast cancer patients causes meaningful consequences. Cardioprotective strategies with CHF medications have shown benefit in limited studies with higher dose anthracycline regimens with a “one hit model.” This study had a relatively low dose of anthracyclines with trastuzumab, a “two hit model.” Cardioprotective agents did not prevent events in this two hit model. Different mechanisms of cardiac injury may be responsible. More randomized studies need to be completed to evaluate the mechanisms of these cardiotoxic agents and possible cardioprotective strategies. As molecular understanding of these cardiotoxic agents improves and imaging technology advances, certain high-risk subgroups may benefit from cardioprotective agents.