Circulating tumor cells (CTC): Assessment of treatment efficacy in metastatic breast cancer (MBC)

Abstract

10535 Background: Preliminary data in MBC suggest that ≥5 CTC/7.5 mL blood is associated with worse progression free survival (PFS) and overall survival (OS), and that the persistence of ≥5 CTC/7.5 mL blood after the initiation of therapy predicts for treatment failure (NEJM 2004. 351:781.). We are conducting a prospective clinical research study to validate the prognostic and predictive significance of this serum biomarker in MBC. Methods: Serial CTC levels are obtained in patients starting a new systemic treatment regimen for progressive, radiographically measurable MBC. 10 mL samples of peripheral blood are collected before the start of treatment and then at 3–4 week intervals. All subjects are followed prospectively for PFS and OS, and they are offered the opportunity to continue CTC testing upon disease progression. CTC enumeration is performed on a 7.5 mL blood volume using the CellSearch technology (Veridex, LLC; Warren, NJ). Epithelial cells are immunomagnetically separated and fluorescently labeled, and nucleated (DAPI+) cells with the EpCAM+, cytokeratin 8/18/19+, and CD45- phenotype are counted as CTC. Clinical outcomes are based on radiographic studies and physical examination in accordance with RECIST criteria. Results: 46 of 100 subjects have been accrued, and 33 have completed at least one radiographic staging evaluation with a median follow up of 7 mos (range 2–18 mos). Treatment for the 33 evaluable patients includes chemotherapy (27%), endocrine therapy (46%), and combination therapy with a biologic agent (27%). At baseline, 85% (28/33) had at least 1 CTC/7.5 mL (range 1–78), and 27% (9/33) had ≥5 CTC/7.5 mL. Median PFS was 2.57 months and 6.77 months for subjects with ≥5 vs <5 CTC/7.5 mL at baseline, respectively (p=0.02). Conclusions: The current data validate the observation that baseline CTC levels correlate with PFS in patients with MBC and measurable disease. Patient accrual and data analysis are ongoing to confirm that persistent CTC levels ≥5/7.5 mL correlate with a lack of treatment efficacy and therefore are a reliable surrogate marker of disease responsiveness and PFS. [Table: see text]