scholarly journals Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer

2017 ◽  
Vol 63 (10) ◽  
pp. 1585-1593 ◽  
Author(s):  
Maren Bredemeier ◽  
Philippos Edimiris ◽  
Pawel Mach ◽  
Mikael Kubista ◽  
Robert Sjöback ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Clinical Staging ◽  
Significant Differential Expression

Abstract BACKGROUND Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC− patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC−. CONCLUSIONS ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.

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.

Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

2015 ◽  
Vol 362 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Wendy Onstenk ◽  
Anieta M. Sieuwerts ◽  
Marleen Weekhout ◽  
Bianca Mostert ◽  
Esther A. Reijm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metastatic Breast ◽  
Primary Tumors

scholarly journals Circulating Tumor Cells: A Useful Predictor of Treatment Efficacy in Metastatic Breast Cancer

2009 ◽  
Vol 27 (31) ◽  
pp. 5153-5159 ◽  
Author(s):  
Minetta C. Liu ◽  
Peter G. Shields ◽  
Robert D. Warren ◽  
Philip Cohen ◽  
Mary Wilkinson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Endocrine Therapy ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Disease Status ◽  
Radiographic Disease

PurposeFive or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.Patients and MethodsSerial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.ResultsSixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.ConclusionWe provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.

scholarly journals The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

2021 ◽  
Vol 10 (4) ◽  
pp. 684
Author(s):  
Lorena Alexandra Lisencu ◽  
Eduard-Alexandru Bonci ◽  
Alexandru Irimie ◽  
Ovidiu Balacescu ◽  
Cosmin Lisencu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Breast ◽  
Cochrane Library ◽  
Mesenchymal Transition

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.

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