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Open Access Highly Access Research article

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

François-Clément Bidard1,2, David Hajage3, Thomas Bachelot4, Suzette Delaloge5, Etienne Brain6, Mario Campone7, Paul Cottu1, Philippe Beuzeboc1, Emilie Rolland3, Claire Mathiot8 and Jean-Yves Pierga1,2*

Author Affiliations

1 Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005 Paris, France

2 Université Paris Descartes, 12 rue de l'école de Médecine, 75006 Paris, France

3 Department of Biostatistics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France

4 Department of Medical Oncology, Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France

5 Department of Medical Oncology, Institut Gustave Roussy, 114 rue Vaillant, 94800 Villejuif, France

6 Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, 35 rue Dailly, 92210 Saint Cloud, France

7 Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Bd Monod, 44800 Saint Herblain, France

8 Hematology laboratory, Institut Curie, 26 rue d'Ulm, 75005 Paris, France

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Breast Cancer Research 2012, 14:R29 doi:10.1186/bcr3114

Published: 13 February 2012

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.