Although breast cancer is a heterogeneous disease, approximately 20% to 25% of patients diagnosed with breast cancer have amplification of the HER2 gene. The FDA approval of trastuzumab for the treatment of HER2-positive (HER2+) metastatic breast cancer in 1998 represented a major breakthrough for patients with HER2+ disease. In 2006, the FDA extended its approval for use in the adjuvant setting. In recent years, trials have been conducted to identify the appropriate duration of therapy in combination with chemotherapy. More recently, trials incorporating newer HER2-targeted therapies have been conducted. Some trials have demonstrated the importance of considering neoadjuvant HER2-directed therapies for selected patients with HER2+ disease, highlighting the fact that achieving pathologic complete response has important prognostic implications. In order to continue treatment and optimize patient safety, the effective and timely management of treatment-related adverse events (AEs) is crucial. As they are on the front lines of patient care, advanced practitioners need to be able to assess the clinical implications of recent advances and integrate them into practice. One area of unmet need in the management of metastatic HER2-positive disease is the treatment of brain metastases, with several promising therapies under investigation. Using several case studies as a foundation, this article highlights current and emerging data on HER2-directed therapies, outlines strategies for managing AEs, and reviews the key issues surrounding brain metastases and associated novel therapies under investigation.
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