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Abstract
IntroductionCirculating 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.MethodsThe 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.ResultsA 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.ConclusionsFor 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.
Highlights
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 progressionfree survival (PFS) in metastatic breast cancer patients
We have recently reported this confirmatory objective of the study, which was clearly reached: CTC changes are a strong prognostic factor for both PFS and overall survival (OS) [9]
For the first time, the comparison of CTC with different serum tumor markers (CEA, cancer antigen (CA) 15-3, CYFRA 21-1) and non-tumor markers, which was a prospectively planned secondary objective of the IC 2006-04 study
Summary
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 progressionfree survival (PFS) in metastatic breast cancer patients. Several serum markers have been developed in different types of cancer as tools for non-invasive assessment of the tumor burden, mostly in metastatic patients. CEA is a cell surface glycoprotein involved in cell adhesion, normally not present in the blood of healthy adults. CA 27.29, mostly used in North America, and CA 15-3, mostly used in Europe, correspond to two different epitopes of the same protein, MUC1, which is a cell surface glycoprotein involved in cell adhesion. The 2007 American Society of Clinical Oncology update on tumor markers in breast cancer [6] reported that for monitoring patients with metastatic disease during therapy, CA 27.29 or CA 15-3 can be used in conjunction with other monitoring tools, such as tumor response radiological assessment
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