Monitoring Apoptosis and BCL-2 on Circulating Tumor Cells (CTC) in Patients with Metastatic Breast Cancer

Jeffrey B. Smerage, G. Thomas Budd, Gerald V. Doyle, Marty Brown, Constanza Paoletti, Maria Muniz, M. Craig Miller, Madeline I. Repollet, David A. Chianese, Mark C. Connelly, Leon W.M.M. Terstappen, Daniel F. Hayes

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Background: Enumeration of circulating tumor cells (CTC) from whole blood permits monitoring of patients with breast carcinoma. Analysis of apoptosis & Bcl-2 expression in CTC might add additional prognostic and predictive information. We estimated the degree of these markers in CTC from patients being treated for metastatic breast cancer.

Methods: Eighty-three evaluable patients initiating a new therapy for metastatic breast cancer were enrolled. Whole blood was collected at baseline, at one of three short term time windows (24, 48, or 72 h) after initiating treatment, and at first follow-up (3–5 weeks). CTC were isolated, enumerated, and expression of M30 and Bcl2 was determined using the CellSearch® System.

Results: At baseline, window, and 3–5 weeks post-treatment, 41/80 (51%), 40/80 (50%) and 21/75 (28%) patients had ≥5 CTC, respectively. At baseline, the proportion of CTC-apoptosis (M30) was inversely correlated with CTC number, and modestly inversely correlated with CTC-Bcl-2. As expected, higher CTC levels at baseline or first follow-up were associated with worse prognosis. Surprisingly, in patients with elevated CTC, higher levels of CTC-apoptosis were associated with worse prognosis, while higher CTC-Bcl-2 levels correlated with better outcomes.

Conclusions: CTC apoptosis and expression of Bcl-2 can be analytically determined in patients with metastatic breast cancer and may have biological and clinical implications. Characterization of CTC for these and other markers could further increase the utility of CTC monitoring patients in clinical investigations of new anti-neoplastic agents.

Original languageEnglish
Pages (from-to)680-692
JournalMolecular oncology
Issue number3
Publication statusPublished - 2013


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