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.

Systemic treatment of HER2+ metastatic breast cancer: Clinical conundrums and future perspectives

“…There are no large series of patients in DCR. However, with increasing time since the advent of trastuzumab for advanced breast cancer, case reports and smaller series are now emerging. Eleven patients with DCR were described in a single institution (Dublin) series, none of whom had received adjuvant trastuzumab.…”

“…Factors associated with DCR are ER negativity, CR following first‐line treatment, no adjuvant trastuzumab and liver only disease . The long‐HER study is analyzing molecular factors associated with DCR and ultimately may allow prediction of which patients may achieve DCR and cease maintenance trastuzumab .…”