Techniques and Thresholds for Quantifying Circulating Tumor Cells in Breast Cancer—In Reply

In Reply Liu and colleagues raised 2 important issues regarding our report on the use of a circulating tumor cell (CTC) assay as a prognostic biomarker for late recurrence in localized, estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer. First, they point out the potential limitations of the CTC assay used in our study, which detects only tumor cells expressing epithelial cell adhesion molecule (EpCAM) and thus does not detect other cell populations that may have greater potential to seed distant sites and contribute to the development of clinically evident metastases. There are more than 50 different CTC assays currently available; they vary in their methodology for detection and cell populations detected and hence vary in their sensitivity and specificity for CTC detection. In 1 of the few reports of a cross-platform comparison of 2 different CTC assays in patients with advanced prostate cancer, 1 assay that detected nonepithelial and epithelial populations exhibited greater clinical sensitivity, higher CTC cell counts, and more robust prognostic information than another assay that detected only an EpCAM-positive population. Additional studies are needed that involve cross-platform comparisons of assays that differ in their detection method and cell populations detected in breast cancer and other cancers.

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