Abstract 3696A: The detection and prediction of circulating tumor cells in breast cancer patients

Abstract The detection of circulating tumor cells (CTC) in the blood of cancer patients is a promising tool for risk stratification, treatment tailoring, and monitoring of the disease state. The current study aims to develop a QPCR-based detection platform for the semi-quantitation of tumor cell load in the peripheral blood of breast cancer patients by combining gene expression data from 4 tumor marker genes into a single index-score. From a cohort of 131 individuals, CTC index-score positivity, indicating tumor cell presence, was observed in 14 out of 16 (88%) metastatic patients, 16 out of 87 (18%) non-metastatic stage I-III patients, and 0 out of 28 (0%) healthy female controls. A previous study demonstrated that CTC index-score positivity in metastatic patients correlated to a significantly shorter time to disease progression. This CTC detection platform demonstrates high specificity (100%) and sensitivity (88%), and can be an effective clinical tool providing valuable prognostic information. This CTC detection assay was subsequently compared to a CTC prediction assay developed using microarray expression data from the primary tumors of the patients from the same cohort. From 73 patients, a CTC predictive tumor profile was developed with the ability to distinguish those patients with a positive CTC QPCR index-score from those with a negative index-score with an average 83% internal cross-validation accuracy. When a small independent test set was assayed, those patients classified on the basis of their tumor gene expression as having a positive CTC QPCR score had a shorter interval to metastasis development (mean = 29.6 months) versus those predicted to have a negative score (mean = 51.4 months). When the QPCR-based and microarray-based CTC assays were compared directly, and each in combination with the “70-gene prognosis signature” for distant metastasis prediction, the CTC predictive microarray assay was superior to the CTC QPCR assay both alone and in combination with the 70-gene profile for time interval to metastasis. This study demonstrates that a microarray model predictive of tumor cell dissemination has prognostic value and seems independent of other metastasis-predictive microarray profiles.