Neoadjuvant and Adjuvant Therapy for HER2 Positive Disease.

Since the initial description of the HER2 proto-oncogene as a poor prognostic factor in breast cancer in 1987, to the first randomized trial of a monoclonal antibody directed against HER2 in combination with chemotherapy for the treatment of metastatic HER2-positive breast cancer published in 2001, to the American Society of Clinical Oncology (ASCO) 2005 Annual Meeting in which we saw the unprecedented collective presentations demonstrating the dramatic benefit of trastuzumab in the adjuvant setting-the clinical landscape of HER2-overexpressing breast cancer has forever changed. More recently, there has been increasing use of preoperative chemotherapy and anti-HER2 targeted therapies in primary operable HER2 disease in the research domain and in clinical practice. In the next few years, we will see if dual adjuvant anti-HER2 antibody inhibition produces clinically significant improvements in outcome; understand if there is a role of small molecule inhibitors of the HER family of receptors either in combination or sequential to trastuzumab; further refine the relationship between pathologic complete response (pCR) and long-term clinical outcomes; and find predictive biomarkers to identify cohorts of patients that may need differential combinations and/or durations of anti-HER2 therapies.