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Introduction:There is a growing body of evidence that the HER2 status can change during disease progression (Gancberg et al. 2003). However, the re-assessment of the HER2 status to evaluate the eligibility for HER2 targeted therapy by a tissue biopsy of the metastatic lesion may not always be feasible. In this context, determination of the HER2 status using CTCs might be a strategy with potential clinical application. So far, no large prospective studies were performed comparing different methods for CTCs detection and characterization. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients using the antibody based CellSearch©assay and the RT-PCR approach AdnaTest Breast Cancer and to assess the concordance rate between these two techniques. Both techniques are frequently used in clinical trials.Method:A total of 252 metastatic breast cancer patients from 9 different certified breast cancer centers (Düsseldorf, Erlangen, Essen, Freiburg, Hamburg, Heidelberg, Muenchen, Regensburg, Tuebingen) were enrolled in this prospective open trial from 01/2008 until 04/2009. HER2 status of CTCs was assessed using both the FDA approved CellSearch©Assay (Veridex, Warren, NJ, USA) and the AdnaTest Breast Cancer (Adnagen, Langenhagen, Germany) according to the manufacturers' instructions. A web based databank was designed for data management and online-documentation (www. detect-study.de). The study design was approved by the ethics' comittee (2007/B01).Results:Using the CellSearch©Assay, 133 of 252 (55%) metastatic patients had CTCs at the time of first diagnosis or disease progression. HER2 positivity was observed in 39% of CTC positive patients (52 of 133) but only 22 of these had initially a HER2 positive primary tumor. Eighty-eight of 225 (39%) patients were CTC positive using the AdnaTest Breast Cancer. The HER2 positivity rate was 47% (41 of 88). Eight of these patients had a HER2 positive primary tumor whereas 33 patients were initially HER2 negative or unknown. Summarizing the data, the rate of breast cancer patients with HER2 negative primary tumors but HER2 positive circulating tumor cells was 38% (32 of 61) and 48% (28 of 41) using the CellSearch Assay and the AdnaTest Breast Cancer, respectively. Considering only those patients who had CTCs on both tests (n=61), the concordance rate regarding HER2 expression was 51% (32 of 61).Conclusion:Based on CTCs the HER2 status can change during disease progression. However, using different techniques, disconcordant results were obtained. To prove the clinical value of these CTC assays and to implement the HER2 status of CTCs as a stratification parameter in future clinical trials, it will be mandatory to correlate clinical response to HER2 targetd therapy on each method in patients with HER2 positive CTCs. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3004.