Abstract
Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson’s r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment.
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Acknowledgments
We thank Venkata Sai Vemula, Louai Hauranieh, and Eduardo Sosa for technical assistance.
Grant support
UCSF Research Allocation Program (M.E. Melisko). The Breast Cancer Research Foundation (M.J.M. Magbanua). Bay Area Breast Cancer Translational (SPORE) P50 CA58207 (J.W. Park).
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The study protocol was approved by the Committee on Human Research at the University of California San Francisco. All patients gave informed consent for participation in this study.
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Jin Sun Lee, Michelle E. Melisko, and Mark Jesus M. Magbanua have contributed equally to this work.
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Lee, J.S., Melisko, M.E., Magbanua, M.J.M. et al. Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer. Breast Cancer Res Treat 154, 339–349 (2015). https://doi.org/10.1007/s10549-015-3610-1
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DOI: https://doi.org/10.1007/s10549-015-3610-1