Abstract 2379: Expression of truncated HER2 receptor in circulating tumor cells (CTCs) of breast cancer patients

Abstract

Abstract Introduction: HER2 receptor is overexpressed in 15-25% of patients with breast cancer. In HER2 positive breast cancer the administration of trastuzumab has changed the outcome of disease. However, most patients will eventually develop resistance to trastuzumab. The presence of a truncated receptor with loss of the extracellular portion of HER2 (p95HER2) has been proposed as a potential mechanism of resistance. Preclinical and clinical data suggest that the expression of p95HER2 is associated with poor overall prognosis, resistance to trastuzumab and sensitivity to lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor. We have recently shown that approximately 50% of breast cancer patients express HER2 in their CTCs (Kallergi et al., 2007; Kallergi et al., 2008). The aim of the present study was to characterize, for the first time, the expression of p95HER2 in CTCs of breast cancer patients. Methods: Triple staining immunofluorescent (IF) experiments were performed in peripheral blood mononuclear cells (PBMC) cytospins of patients with early (n=24) and metastatic (n=33) breast cancer who were CK-19 mRNA-positive by real time PCR. Pancytokeratin A45-B/B3 antibody (as a marker of CK-positive cells) was coupled with antibodies against the extracellular and the intracellular domains of HER2. Slides were analysed with either confocal laser scanning microscopy or with the Ariol system. Results: Cytokeratin positive cells were identified in 17 (71%) out of 24 early and in 20 (61%) out of 33 metastatic patients. HER2 positive CTCs were identified in 53% of early and 50% of metastatic CTC-positive breast cancer patients. HER2-positive CTCs lacking the extracellular domain of the receptor (p95HER positive CTCs) were identified in 35% of metastatic and 12% of early breast cancer patients. Exclusively p95HER2 positive CTCs were detected in 12% of patients with metastatic but not in patients with early disease. Conclusions: These data suggest that the truncated p95HER2 receptor is expressed in CTCs of both early and metastatic breast cancer patients. This finding has important therapeutic implications and may explain the observed increased efficacy of the trastuzumab plus lapatinib combination in HER2 positive breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2379. doi:1538-7445.AM2012-2379