1089 Background: The “invisible” potential of a tumor is responsible for the discrepancy sometimes observed between favourable initial pathological profile and aggressive clinical course. We describe a series of Breast Cancer patients with refractory to standard chemotherapy advanced tumors without HER2-amplification/overexpression treated with trastuzumab (TZB). Methods: Twenty five patients progressing under anthracyclines and taxanes were selected on the basis of increased HER2-ECD levels at entry (>16 ng/ml) and lack of HER2-amplification/overexpression in the primary tumor documentation. In 22/25, TZB 6 mg/m2 with either docetaxel 75 mg/m2 q3w or paclitaxel 90 mg/m2 weekly were administered for six courses or less if toxicicity or progression was documented; TZB alone had to be continued thereafter until progression. Serial HER2-ECD were performed during therapy. Results: No objective response was noted; however, in 5 and 11 pts minor response and stabilization respectively was noted. All minor responders and stabilized patients experienced subjective improvement. Toxicity was acceptable. Median time to progression has not yet been reached, actually 5+mos; in 9 patients the progression-free period is 12 months from start of therapy. Median HER2-ECD declined from 54ng/ml at baseline to 14.3ng/ml at 28 weeks from treatment start. Conclusion: Although the sample size of this case-series is small, our findings suggest that, in HER2 negative patients with clinical aggressive behaviour and refractoriness to standard chemotherapy, HER2 positivity should be assessed by serum ECD levels and the addition of trastuzumab may be a valuable therapeutic option. However, these findings should be confirmed in larger number of patients. No significant financial relationships to disclose.