 We have completed the first single-agent neoadjuvant trastuzumab study in human breast cancer. The specific aims of this study were to firstly, define the clinical efficacy of trastuzumab, and secondly, to determine its mechanism of action in human breast cancer specimens. From September 1999 to June 2003, 27 patients with HER2 overexpressing locally advanced breast cancer with or without gross metastatic disease, were considered for a phase II study with neoadjuvant trastuzumab. At presentation, the median tumor size was large at 8x8 cm2 range 4x4 cm2 to 25x20 cm2. We did not expect measurable evidence of tumor regression with this short treatment duration. However, regression in the product of bidimensional tumor measurements with a median decrease of -20.0 range 0, -60.4, p0.0001 was observed in primary tumors after only 3 weeks of single agent trastuzumab. Most surprisingly, partial response was observed in 26 727. Minor response was seen in 44 1227, and stable disease in 30 827. No tumors increased in size during this 3-week period. 