The Long-HER study: Clinical and molecular analysis of advanced HER2+ breast cancer treated with trastuzumab and associated to long-term survival.

Abstract

608 Background: Some patients with advanced HER2+ breast cancer survive in the long-term after receiving trastuzumab-based therapy. Long-HER study was an observational, multicenter study that compared long-term survivors and a control group from the clinical and molecular point of view. Methods: Patients with metastatic HER2+ breast cancer that had been treated with trastuzumab-based therapy and had an objective response or stable disease for at least 3 years were included. A control group having a progression in the first year of therapy was selected for comparison (similar first-line therapy). A microarray platform was used to assess whole genome expression analysis in paraffin-embedded samples. Differential expression, ontology and analysis of metabolic pathways were performed. Results: 103 patients were registered, 71 of who had a long-term complete remission. Only 5 of these patients had received trastuzumab in the adjuvant setting: this was the only clinical factor associated to long-term survival. The molecular study included 35 Long-HER and 18 control samples. Gene expression ontology revealed alterations in HIF, apoptosis, and EGF, PI3K and p53 pathways. The PI3K pathway was mostly related with a poor response to therapy. Conclusions: trastuzumab-based therapy achieves long-term survival in a selected group of women with advanced HER2-positive breast cancer. Whole genome analysis comparing such a group with a control group found some alterations that may predict early progression to trastuzumab.