Circulating tumor cell detection: A direct comparison between the CellSearch System, the AdnaTest, and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22117-e22117
Author(s):  
L. Y. Dirix ◽  
H. Elst ◽  
I. Benoy ◽  
I. Van der Auwera ◽  
A. Prové ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Rt Pcr ◽  
Cellsearch System ◽  
Blood Samples ◽  
Detection Techniques ◽  
Qrt Pcr ◽  
Pcr Assays

e22117 Background: The detection, enumeration and isolation of circulating tumor cells (CTC) has considerable potential to influence the clinical management of patients with breast cancer. There is however a substantial variability in the rates of positive samples using existing detection techniques. Methods: This study was designed to compare three techniques for detecting CTC in blood of 80 patients with metastatic breast cancer (MBC) and 20 healthy controls: the CellSearch System, which is an automated, standardized and regulatory-approved system for the immunocytochemical detection and quantification of CTC in blood; ii) the AdnaTest Breast Cancer Select/Detect, which involves the detection of tumor-associated transcripts by RT-PCR after an immunomagnetically enrichment of tumor cells; iii) an in-house developed multimarker qRT-PCR assay, which involves the quantification of tumor-associated transcripts (CK-19 and MAM) by qRT- PCR. Results: As a result, 23% of patients with MBC were positive by the CellSearch System (≥5 CTC), 22% by the AdnaTest (>0.30 ng/μl for any of the amplicons), 31% by qRT-PCR for CK-19 and 49% by qRT-PCR for MAM. Samples were more likely to be positive by qRT-PCR for at least one mRNA marker than by the CellSearch System (P<0.001) or the AdnaTest (P <0.001). The concordance between samples analyzed by the CellSearch System and the AdnaTest was substantial (κ = 0.667, P <0.001). Agreement between both detection techniques was observed in 88% of blood samples. When the CellSearch System was compared with the qRT-PCR assays for CK-19 and MAM, we observed agreement percentages of 78% and 58%, respectively (κ = 0.462, P <0.001 and κ = 0.159, P = 0.09). Agreement between the AdnaTest and the qRT-PCR assays for CK-19 and MAM was observed in 78% and 53% of blood samples, respectively (κ = 0.443, P <0.001 and κ = 0.05, P = 0.607). Conclusions: We observed a substantial variation in the detection rates of CTC in blood from MBC patients using three different techniques. A higher rate of positive samples was observed using a combined qRT-PCR approach for CK-19 and MAM, which suggests that this is currently the most sensitive technique for detecting CTC. No significant financial relationships to disclose.

scholarly journals Circulating Tumor Cells in Metastatic Breast Cancer: Clinical Applications and Future Possibilities

2020 ◽  
Vol 10 (9) ◽  
pp. 3311
Author(s):  
Maggie Banys-Paluchowski ◽  
Florian Reinhardt ◽  
Tanja Fehm
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Study Groups ◽  
Clinical Applications ◽  
Response To Treatment ◽  
Cellsearch System

Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast cancer, detection of CTCs correlates with clinical outcome in early and metastatic settings. CTC persistence beyond first cycle of palliative chemotherapy indicates poor response to treatment in metastatic situation. Beyond prognostication and therapy monitoring, CTC counts can guide treatment decisions in hormone receptor positive HER2-negative metastatic breast cancer. Furthermore, CTC-based therapy interventions are currently under investigation in clinical trials. In this review, we focus on the current state of knowledge and possible clinical applications of CTC diagnostics in patients with metastatic breast cancer.

Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20033-20033
Author(s):  
N. Fersis ◽  
V. Deckwart ◽  
A. Leitz ◽  
M. Weber ◽  
J. Rom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Her 2

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.

Relevance of circulating tumor cells (CTC) in the progression of metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21066-21066
Author(s):  
A. Altimari ◽  
S. Quercia ◽  
E. Benedettini ◽  
M. Rosati ◽  
E. Capizzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Molecular Probes ◽  
Cytokeratin 19 ◽  
Blood Samples

21066 Background: metastatic breast cancer is an incurable disease. Molecular tumor staging methods are required for a better therapeutic approach. Patients and Methods: eight mL blood samples were drawn from 20 patients (pts) (mean age 61.9±9) with metastatic breast cancer at the time of the beginning of a new chemo- or hormonal treatment line. Median follow-up was 7±4.5 months. Twenty- five female healthy blood donor volunteers were used as controls. Blood samples were screened for the presence of circulating tumor cells (CTC) with a quantitative PCR method using molecular probes for human mammaglobin (hMAM) and cytokeratin 19 (CK19). Relative quantification of hMAM and CK19 RNA was obtained using a blood sample infected with known concentrations of MDA-MB453 cells as calibrator. Results: none of the healthy controls was hMAM positive while the cut-off for CK19 was calculated as the mean value of the controls plus two standard deviations. Nine of 20 (45%) pts were hMAM positive, 15/20 (75%) CK19 positive, while 18/20 (90%) pts were positive for at least one marker (CTC positive). Among the 14 (70%) pts who had a disease progression 7 died. Seven of 9 hMAM positive (78%) and 11/15 (73%) CK19 positive pts had disease progression. All the 14 pts who had disease progression were CTC positive while the only 2 CTC negative pts were free from progression at the time of last follow-up. Conclusions: (1) Multiple (hMAM, CK19) rather than single marker detection should be preferred for CTC blood screening in breast cancer. (2) Combined hMAM and CK19 evaluation might identify pts at higher risk of tumor progression and might be useful for stratification and decision making in metastatic breast cancer pts. No significant financial relationships to disclose.

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