American journal of clinical oncology
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Am. J. Clin. Oncol. · Apr 2010
ReviewTrastuzumab-based therapy for patients with HER2-positive breast cancer: from early scientific development to foundation of care.
Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression occurs in 20% to 25% of breast tumors, often leading to an aggressive disease course and poor clinical outcomes. Successful targeting of HER2-positive tumors in preclinical models with trastuzumab has translated to the clinic. In HER2-positive metastatic breast cancer (MBC), trastuzumab provides significant clinical benefit as a monotherapy and in combination with numerous chemotherapies. ⋯ Clinical success in the metastatic setting provided the rationale for assessing trastuzumab in early breast cancer. Four large trials of adjuvant trastuzumab demonstrated significant improvements in disease-free survival (33%-52%) and overall survival (34%-41%) despite tumor size, nodal or hormone-receptor status, and age. New approaches to maximize the clinical benefit of trastuzumab-based therapy are under investigation and include novel combinations with other targeted therapies such as bevacizumab, pertuzumab, and lapatinib.