Adjuvant HER2-Targeted Therapy Update in Breast Cancer: Escalation and De-escalation of Therapy in 2018

Purpose of Review: The introduction of trastuzumab for the adjuvant treatment of tumors with amplification of HER2/neu has been one of the most exciting advances in systemic treatment in the history of breast cancer and has transformed the natural history of HER2/neu-positive (HER2+) breast cancer (BC). There have been several recent advances in the adjuvant treatment of HER2+ BC and herein we review recently reported clinical trials focusing on the impact of expanding therapeutic options with attention to optimal sequence of the available treatment options and clinical aspects of escalating or de-escalating therapy for patients based on their level of risk. Recent Findings: Two major clinical trials (APHINITY and EXTENET) reported modest improvements in disease-free survival (DFS) leading to FDA approval of pertuzumab in the adjuvant setting and neratinib in the extended adjuvant setting for HER2+ BC. In addition to the previously established utility of trastuzumab in combination with chemotherapy in the adjuvant setting, we now have expanded options with two additional agents. However, it has become challenging to appropriately sequence therapies and select patients who will truly benefit from receipt of additional therapies and for which patients de-escalation of therapy may be possible. Summary: Although significant advances have been made in the treatment of HER2+ BC since the introduction of trastuzumab over the past 20 years, patients do still harbor primary resistance and experience recurrence following optimal treatment. In this review, we seek to provide a practical approach for clinicians to optimally utilize the available adjuvant anti-Her2 drugs with the data currently available.