Targeting HER-2 pathway in presence of cardiac dysfunction: the walk on a tight rope

Abstract Human epidermal growth factor receptor 2 (HER2) is overexpressed in 25%–30% of breast cancer cases and was previously correlated with inferior outcomes. HER2 amplification in breast cancer was discovered in the 1980’s and the monoclonal antibody has largely been available for clinical use since the 2000’s. Introduction of HER2-targeted therapies like trastuzumab into treatment paradigm has markedly improved survival outcomes but cardiac dysfunction is a well-known adverse effect. Despite more than two decades of targeting HER2 pathway, the appropriate use of anti-HER2 agents in a patient with pre-existing cardiac dysfunction has not been conclusively established. This report describes management of early-stage HER2-positive breast cancer in a 65-year-old woman with pre-existing cardiomyopathy. Contraindications to use of HER2-targeted monoclonal antibodies prompted the use of lapatinib, an oral tyrosine kinase inhibitor (TKI) with relatively shorter half-life, absence of antibody dependent cellular cytotoxicity and lower incidence of cardiotoxicity. Because it is taken orally, lapatinib allows for dose adjustments and even interruption in case of adverse event. This allows for rapid withdrawal of its effect on the heart making it favorable compared to use of trastuzumab in this context. Our patient, receiving neoadjuvant chemotherapy with lapatinib, demonstrated a complete metabolic response on imaging without worsening cardiac dysfunction. This case report highlights a gap in literature regarding the management of HER2-positive breast cancer in patients with pre-existing cardiac dysfunction, while also offering guidance for potential future use of TKIs as HER2-directed therapy in this population.