Predictive Value of Circulating Tumor Cells (CTCs) in Metastatic Breast Cancer Patients Treated by Bevacizumab-Based Therapy.
Authors: Mego M. , Mego M. , Mego M. , De Giorgi U. , De Giorgi U. , Hsu L. , Dawood S. , Andreoupolou E. , Valero V. , Handy B. , Ueno N. , Reuben J. , Cristofanilli M. 
Published: December 2010

Background:Circulating tumor cells (CTC) are involved in cancer dissemination and are an independent prognostic factor in metastatic breast cancer (MBC). Antiangiogenic, bevacizumab-based chemotherapy improves response rate and progression free survival in patients with metastatic breast cancer (MBC), without impact on overall survival. Preclinical data suggest the possibility of increased metastatic potential of tumor cells pretreated by anti-angiogenic therapy (Ebos et al. Cancer Cell 2009,15: 232–9). The aim of this study was to determine the prognostic value of CTC in MBC patients treated by bevacizumab-based therapy.Patients and Methods: This retrospective study included 48 MBC treated with bevacizumab combined chemotherapy regimens and 46 patients treated with chemotherapy alone between January 2004 and December 2008 at M.D.Anderson Cancer Center. CTCs were detected and enumerated before patients started therapy using the CellSearch™ system (Veridex, LLC, NJ, USA). Progression free survival (PFS) and overall survival (OS) were calculated from the date of CTC measurement, estimated by the Kaplan-Meier product limit method, and compared between groups with the log-rank test.Results: At a median follow up of 10.1 months (range: 1-26 months), 22 patients (45.8%) had died. The estimated medians of PFS in bevacizumab-treated patients were 8.1 vs. 5.2 months (p = 0.42) in patients with baseline &lt; 5 CTCs vs. ≥ 5 CTCs. Moreover, the OS for the two subgroups were 18.3 vs. 12.4 months (p = 0.41), respectively. Twenty-three patients had CTC measurements at the time of progression. Median CTC counts at baseline and at time of disease progression were 6 (range: 0-230) and 7 (range: 0-359) respectively in the bevacizumab-treated group. The median CTC counts in the control group at same time points were 7 (range: 0-724) and 2 (range:0-999), respectively. Thirteen (56.5%) and 12 (52.2%) patients had CTC ≥ 5 at baseline and at time of disease progression in bevacizumab-treated group compared to CTC counts of 24 (52.2%) and 17 (37%) in control group treated with chemotherapy without bevacizumab. Post progression overall survival in patients with CTC &lt; 5 and CTC ≥ 5 measured at time of disease progression were 11.0 and 10.4 months (p = 0.36), in the bevacizumab treated group vs. 27 and 12.4 months (p = 0.04), in the control group respectively.Conclusion: Our data support the prognostic value of CTC measured before therapy in MBC. The detection of higher CTC counts at time of disease progression and the limited prognostic value of CTC after failure of bevacizumab-based chemotherapy although intriguing, warrants further prospective investigations. Moreover, a comparison between the differential effects of monoclonal antibodies and tyrosine kinases inhibitors on CTCs detection and monitoring will better clarify the role of specific targeted therapies on micrometastatic disease.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3013.