Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or gene amplification is found in up to 20% of breast cancers, whereas 50% have low HER2 expression levels. The natural history of HER2-positive (HER2+) disease has been profoundly transformed by HER2-targeted agents and antibody-drug conjugates (ADCs). With the recent US Food and Drug Administration (FDA) approval of a novel HER2-directed ADC, trastuzumab deruxtecan (T-DXd), in both HER2+ and HER2-low metastatic breast cancer (MBC), potential treatment options have expanded for these patients.
For practicing community clinicians, this evolution of HER2-directed therapy and targeting the full spectrum of HER2 expression threatens to add additional complexity in treatment selection and sequencing across lines of therapy. The increasing array of HER2-directed approaches challenges clinicians to stay abreast of clinical data and understand how to implement this evidence in daily practice. This session will assist clinicians in determining how these novel agents fit into treatment paradigms. This educational activity will address the implications of HER2-expression patterns on treatment selection and planning, explore the effective use of evolving therapeutic strategies, and review the latest clinical data on efficacy and safety as well as evidence-based guideline recommendations.