A QPCR-Based Circulating Tumor Cell Detection Platform Predicts Survival in 776 Early Stage Breast Cancer Patients.

Abstract

Abstract The detection of circulating tumor cells (CTCs) in the blood of cancer patients is a promising tool for risk stratification, treatment tailoring, and monitoring of the disease state. We previously developed a QPCR-based platform for the detection of CTCs in peripheral blood, which proved to be prognostic in a cohort of metastatic breast cancer patients.In the current study, we aimed to build on this work by determining the prognostic value of our CTC assay in an independent, prospectively collected, retrospective patient series of 776 non-metastatic, stage I-III breast cancer patients (median follow-up 7.3 years). Assay positivity was observed in 83 patients (10.7%), while maintaining 96% specificity in a group of 25 healthy female controls (however a second blood sample from the healthy control that gave a positive result was found to be negative). CTC positivity as determined by our assay corresponded to a significantly poorer relapse-free survival (RFS) (HR = 1.9, 95% CI = 1.3-2.9, p = 0.02) and overall survival (HR = 1.8, 95% CI = 1.1-2.8, p = 0.02) in this group. This platform demonstrated similar prognostic power to the pan-anticytokeratin (AE1/AE3) immunohistochemistry-based detection of disseminated tumor cells (DTCs) in the bone marrow of these patients (RFS HR = 1.9, 95% CI = 1.3-2.7, p = 0.02). Importantly, multivariate analyses including tumor size, histological grade, lymph node status, and hormone receptor status, both CTC and DTC status remained significant, independent predictors of RFS (CTC status HR = 1.6, 95% CI = 1.0-2.6, p = 0.037; DTC status HR = 1.6; 95% CI = 1.1-2.5, p = 0.023). However, CTC status was prognostic in both lymph node negative patients (HR = 2.0, p = 0.04) and lymph node positive patients (HR = 1.7, p = 0.043), whereas DTC status was only prognostic in lymph node positive patients (HR = 2.0, p = 0.002).This CTC detection platform represents an objective assay with both high specificity and prognostic power, and could be an effective clinical tool for outcome prediction in breast cancer patients.This work was supported by the Sixth Framework Program of the European Commission as part of the international DISMAL collaboration for research into disseminated epithelial malignancies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3002.