HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that 
mediate growth, differentiation and survival of cells. HER-2 overexpression and 
amplification occurs in approximately 15 to 25 % of breast cancers and is 
associated with aggressive tumour behaviour. Herceptin (trastuzumab), a 
humanized monoclonal antibody directed against the extracellular domain of the 
HER-2 receptor, has been shown to have clinical activity in HER-2-positive 
advanced breast cancer when administered alone or in combination with 
chemotherapy. It has been approved for HER-2-positive metastatic breast cancer 
by the United States Food and Drug Administration in 1998 and in the countries 
of the European Union in 2000. Recently, promising results of the four 
randomized international multicenter trials evaluating the therapeutic benefit 
of Herceptin in the adjuvant treatment of HER-2-positive primary breast cancer 
have been reported. Data of the first planned interim analysis of the studies 
showed significantly improved disease-free survival in patients assigned to one 
year of Herceptin compared to the control groups even after short term follow 
up. These results caused an immediate wave of demand for Herceptin in adjuvant 
therapy. Results of these studies are critically reviewed. Furthermore, the 
available preliminary results from studies using Herceptin in the primary 
(neoadjuvant) therapy of HER-2-positive breast cancer are addressed and possible 
implications for HER-2 testing are discussed.