Compartmentalization of tumor cells to the CSF or peripheral blood of a breast cancer patient with CNS metastasis.

Abstract

e11544 Background: We recently adapted the CellSearch system to detect cerebrospinal fluid tumor cells (CSFTCs) in breast cancer patients with CNS metastases and found that the CSFTCs correlate with disease burden. Here, we present the enumeration of CSFTCs and peripheral blood tumor cells (PBTCs) in a patient with metastatic breast cancer during treatment with intrathecal (IT) chemotherapy. Methods: We enumerated CSFTCs and PBTCs in a patient with ER+, Her2-, BRCA2+ breast cancer and CNS metastases who received IT chemotherapy and systemic chemoradiation. The patient was initially diagnosed with locally advanced breast cancer and underwent bilateral mastectomies followed by AC-T one year prior to CNS relapse. Tumor cell enumeration was conducted every 1-2 weeks from 7.5mL of peripheral blood or 9mL of CSF along with CSF cytology, Karnofsky performance status (KPS), neurologic examination and radiographic studies during the IT chemotherapy and subsequent systemic chemoradiation. Results: At the beginning of the IT chemotherapy the patient presented with diplopia, gait ataxia, 7th facial nerve palsy, confusion, and intractable headaches, an initial burden of 19570 CSFTCs and 10-45 PBTCs, a KPS of 80, and no systemic disease. Tumor cell counts dropped rapidly in response to IT therapy alone to 0-1 CSFTCs and 3 PBTCs, all neurologic symptoms resolved, and the KPS increased to 90. The patient subsequently suffered progression of systemic disease with development of bone and brachial plexus metastases. PBTCs rose from 3 to 64 during this same period, whereas CSFTCs remained at 0-1. The CA 27-29 level increased from 111 to 214. CSF cytology and neuro-radiographic imaging cleared in the face of progressive systemic disease. Conclusions: There was a compartmentalization of metastatic tumor cells to either the blood or the CSF in this patient. We hypothesize that tumor cells in the CSF or peripheral blood migrate to the untreated compartment during compartmentalized therapy, resulting in disease recurrence in the untreated compartment. Preliminary data on other patients supports this hypothesis, which may represent an important mechanism for disease recurrence in patients with potentially curable disease.