COURSE OVERVIEW
Among breast cancers diagnosed at any stage, 20-30% are found to have amplification of the human epidermal growth factor receptor (HER)-2/neu gene by in situ hybridization. This amplification results in the overexpression of a 185-kDa transmembrane protein with tyrosine kinase activity that belongs to the ErbB family. Overexpresslon of this protein, usualy demonstrated by immunohistochemistry (IHC), is associated with adverse disease prognosis and a worse response to treatment. In vitro and animal model experiments provided compelling evidence that targeting the signaling pathway activated by HER-2 could have significant anti-proliferative effects on breast cancers and guided the clinical development of several anti-HER-2 antibodies. Among those, trastuzumab, a humanized monoclonal anti-HER-2 antibody, demonstrated significant activity in patients with heavily pretreated HER-2-positive metastatic breast cancer in early-phase studies. In a seminal phase III, the combination at trastuzumab with first-line chemotherapy resulted in a significant survival benefit when compared with chemotherapy alone. That study also revealed that trastuzumab, especially in combination with anthracylines, was associated with cardiac toxicity. These impressive results provided strong support the conduct of several randomized controlled studies evaluating trastuzumab in combination with chemotherapy in the adjuvant setting. A systematic review and meta-anaIysis was conducted to estimate the benefits and risks of trastuzumab administration with or folIowing chemotherapy for early-stage breast cancer.
LEARNING OBJECTIVES
After successfully completing this certified course, the participant should be able to:
• Summarize the main characteristics and findings of randomized controlled trials evaluating trastuzumab for the adjuvant treatment of early stage breast cancer.
• Use combined effect estimates provided by meta-analysis to appraise the risks and benefits of trastuzumab treatment in the adjuvant setting .
• Identify the links between basic science and drug development that led to the successful clinical use of trastuzumab.