Circulating tumor cells (CTC) can provide the basis for a real-time liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTC. Her-2 assessment of CTC was performed using the CellSearch® system in 103 metastatic (M1) and 88 non metastatic (M0) breast-cancer patients. Digital images of Cytokeratin-PE, DAPI, CD45-APC, and Her-2-FITC from these samples were stored. Expression of Her-2 on CTC was determined by manual review and an automated algorithm using Her-2-FITC fluorescence of leukocytes to determine the Her-2-expression threshold in each sample. Her-2 expression of CTC varied greatly within and between patients compared to Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTC in patients with >5 CTC showed a relatively low discrepancy rate between the primary tumor and CTC Her-2 status. Applying this threshold, 9% of M1 patients with Her-2 negative primary tumors had Her-2 positive CTC status and 29% of M1 patients with Her-2 positive primary tumors had Her-2 negative CTC status. No Her-2 discrepancy was observed between CTC and primary tumor in M0 patients. Our findings demonstrate the feasibility of real-time quantitative and reproducible assessment of treatment targets on CTC, opening a path towards personalized treatment. Her-2 expression is heterogeneous among CTC within each patient. Overall, M1 patients with Her-2 positive primary tumors exhibited Her-2 negative CTC frequently, whereas discrepancies in Her-2 status were limited in other clinical settings.

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 2368. doi:1538-7445.AM2012-2368