Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Abstract

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2009, 122 (1), pp.211-217. <10.1007/s10549-009-0668-7>. <hal-00535421> EPIDEMIOLOGYModeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer Abstract Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (Pvalue \ 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.

Detection of Circulating Tumor Cells in Breast Cancer Patients: Prognostic Predictive Role

“…It was recommended that more than a single cut-off point for positivity of CTC should be used for better risk classification especially in adjuvant trials because there has been no defined threshold point for CTC positivity in this group (Tibbe et al, 2007). It was reported that as CTC levels increased as a continous variable, there was a non linear risk of death in a study of 80 metastatic breast cancer patients (Botteri et al, 2010).…”

Information from CTC measurements for metastatic breast cancer prognosis—we should do more than selecting an “optimal cut point”

“…In the current article by Botteri et al [1] CTCs were determined in 80 metastatic breast cancer patients by the CellSearch TM assay. Four categories of CTC values (0 cells, 1-4 cells, 5-20 cells and more than 20 cells) were defined and then related to progression-free and overall survival.…”

“…Fifty to 80% of metastatic patients have circulating tumor cells in the blood circulation [1][2][3]. The most currently used approach for CTC detection is the CellSearch TM system which is an semiautomated device based on immunofluorescence and flow cytometry.…”

“…Cristofanilli et al [1] used the first 102 patients (training set) from a prospective multi-center trial to select a cutoff point for CTC count to stratify patients into two groups with good or poor clinical outcome and used the 75 subsequently enrolled patients as a validation set. Aiming for the clearest separation, thresholds of 1-10,000 CTCs were systematically investigated in the training set, with progression-free survival (PFS) as outcome of interest.…”

A versatile method for enumeration and characterization of circulating tumour cells from patients with breast cancer

“…[1][2][3][4] Various studies have demonstrated the presence of CTCs in peripheral blood of patients and their association with tumor progression and metastatic development. [5][6][7] Reports have also shown that a change in CTCs number predicts response to therapy and can evaluate residual disease.…”