Abstract P3-02-05: Evaluation of Gene Transcripts in Primary Tumors at Time of Diagnosis and Circulating Tumor Cells (CTCs) at Time of Metastatic Disease

Abstract Introduction: The enumeration of CTCs has already shown to bear clinical relevance as a prognostic and predictive factor in metastatic breast cancer. In addition to enumeration, isolation of CTCs enables their molecular characterization and thus holds great promise to establish association of their genetic profile with patient outcome and to identify potential drugable targets. In this study we established epithelial-specific mRNA and microRNA profiles in CTCs of patients with metastatic breast cancer, compared these profiles to the profiles measured in corresponding primary tumors, and determined their association with clinical parameters. Study design: For this study we included 50 breast cancer patients, of which 32 presented themselves with over 5 CTCs at the time of metastatic disease. From 14 of these patients with more than 5 CTCs at the time of metastatic disease also the primary tumor at time of breast cancer diagnosis was evaluated. Total RNA was extracted 1) from blood of the 50 patients with metastatic disease after EpCAM-based enrichment of 7.5 mL whole blood with the CellSearch™ Profile Kit [Veridex LCC], 2) from 14 unprocessed whole blood preparations from healthy blood donors, and 3) from 14 primary tumors. Gene transcript levels of CTC-specific and potentially clinically relevant mRNAs and microRNAs were compared in CTCs isolated at time of metastatic disease and the corresponding primary tumors. In addition, the association of these transcript levels with clinical data was assessed. Results: We identified 24 mRNA and 14 microRNAs more abundantly expressed in CellSearch-enriched fractions from patients with at least 5 CTCs compared with those without CTCs and/or compared with unprocessed whole blood prior to CellSearch enrichment (Mann-Whitney U-test P<0.05). In addition, when comparing transcript levels present in CTCs during metastatic disease and those measured in the corresponding primary tumor, potentially clinically relevant discrepancies were observed. Findings of interest included changes in transcript levels of genes such as ESR1, ERBB2, TOP2A and MGB1, and in genes associated with proliferation and EMT. Finally, associations were observed between transcript levels measured in CTC preparations and clinical data like nodal status and size of the primary tumor. Conclusion: Our results show that molecular characterization of CTCs is feasible and has potential for a more tailored clinical approach above CTC enumeration in the treatment of metastatic breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-05.