Abstract 3483: Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients.

Abstract

Abstract The enumeration of circulating tumor cells (CTCs) using the CellSearch system (Veridex LLC) is a valuable prognostic clinical tool in several epithelial malignancies. Surveillance methods for metastatic disease involving the central nervous system (CNS) lack adequate sensitivity, specificity, and reproducibility in the clinic. We previously reported a method to enumerate CTCs in the cerebrospinal fluid (CSF) of breast cancer patients with metastases involving the CNS. The enumeration of CTCs in CSF by this method is highly sensitive, accurate, reproducible, and correlates with disease burden by several measures. Here, we concomitantly monitor CTCs in the peripheral blood and CSF of five patients with neoplastic meningitis receiving intrathecal (IT) chemotherapy. In each patient, CTC counts have been more sensitive than conventional cytology, and have predicted the course of symptoms and overall survival more precisely than conventional cytology. We observed a striking inverse relationship between CTC counts in the peripheral blood and CSF. This observation generated the hypothesis that CTCs migrate from the blood to the CSF and the converse as sanctuary sites during compartmentalized therapy to result in systemic disease recurrence. To test this hypothesis we created mouse models of these clinical phenomena including injection of triple-negative breast cancer into the peripheral blood or intracranially. Injection of luciferase-infected MDA-MB-231 or MDA-MB-468 human triple-negative breast cancer cells into the brain of athymic nude mice resulted in primary tumors at the site of injection. The MDA-MB-231, unlike the MDA-MB-468, generated detectable tumor cell dissemination into the CSF of inoculated mice that correlated with a significantly declined survival. CSF collected from the cisterna magna of inoculated mice corroborated these observations. Current studies are examining the impact of compartmentalized therapy on the migration of these tumor cells as well as profiling unique genetic drivers of the subset of tumors cells that disseminate into the CSF. The intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence, and suggests that concurrent systemic and CNS-directed therapy may be warranted. Citation Format: Joshua E. Allen, Akshal S. Patel, David T. Dicker, Jonas M. Sheehan, Michael Glantz, Wafik S. El-Deiry. Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3483. doi:10.1158/1538-7445.AM2013-3483