Optimizing HER2-Directed Therapy in Early-Stage Breast Cancer

Purpose of Review: HER2-positive early breast cancer has been revolutionized by the development of HER2-directed therapy, which has significantly reduced breast cancer recurrence risk and improved overall survival. Here, we review the available treatment options for this patient population and discuss how we might individualize therapy in the future to optimize the balance of efficacy and toxicity. Recent Findings: The addition of pertuzumab to a trastuzumab-based adjuvant regimen improves pathologic complete response rates and invasive disease-free survival (DFS). Addition of neratinib for patients with high-risk disease also contributes to improved DFS. Summary: Current data supports use of dual HER2-directed therapy in combination with chemotherapy, as well as extended HER2-directed therapy (beyond 1 year), in those with high-risk HER2-positive early breast cancer. Ongoing studies aim to identify biomarkers of response and resistance to standard approaches, as well as identify those who might benefit from a chemotherapy-free treatment paradigm.