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Multicenter Study
. 2012 Feb 13;14(1):R29.
doi: 10.1186/bcr3114.

Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study

François-Clément Bidard  1 , David Hajage, Thomas Bachelot, Suzette Delaloge, Etienne Brain, Mario Campone, Paul Cottu, Philippe Beuzeboc, Emilie Rolland, Claire Mathiot, Jean-Yves Pierga
Affiliations
Multicenter Study

Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study

François-Clément Bidard et al. Breast Cancer Res. .

Abstract

Introduction: Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date.

Methods: The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and overall survival (OS). A secondary pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15-3), CYFRA 21-1), and of serum non-tumor markers (lactate deshydrogenase (LDH), alkaline phosphatase (ALP)) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes.

Results: A total of 90% of the patients had at least one elevated blood marker. Blood markers were correlated with poor performance status, high number of metastatic sites and with each other. In particular, CYFRA 21-1, a marker usually used in lung cancer, was elevated in 65% of patients. A total of 86% of patients had either CA 15-3 and/or CYFRA 21-1 elevated at baseline. Each serum marker was associated, when elevated at baseline, with a significantly shorter PFS. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and weeks 6 to 9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction.

Conclusions: For the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15-3, CYFRA 21-1 is commonly elevated in metastatic breast cancer and has a strong prognostic value.

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Figures

Figure 1
Figure 1
Boxplot of CTC and serum markers values (semi log scale), median and CI 95%.
Figure 2
Figure 2
Progression-free survival (PFS) according to blood markers at diagnosis.
Figure 3
Figure 3
PFS according to blood markers before cycle 2.
Figure 4
Figure 4
PFS and marker changes between baseline and cycle 2.
Figure 5
Figure 5
PFS and marker changes between baseline and cycles 3 to 4.
See this image and copyright information in PMC

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