Prognostic impact of circulating tumor cells assessed with the CellSearch System™ and AdnaTest Breast™ in metastatic breast cancer patients: the DETECT study.
BACKGROUND
There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies.


METHODS
In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions.


RESULTS
With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p<0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS.


CONCLUSIONS
The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer.


BACKGROUND
Current Controlled Trials Registry number ISRCTN59722891.
Volkmar
V
Müller
Sabine
S
Riethdorf
Brigitte
B
Rack
Wolfgang
W
Janni
Peter A
PA
Fasching
Erich
E
Solomayer
Bahriye
B
Aktas
Sabine
S
Kasimir-Bauer
Klaus
K
Pantel
Tanja
T
Fehm
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D016017:Odds Ratio; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012307:Risk Factors
D014408:Biomarkers, Tumor