Abstract P4-06-10: Immune related gene expression to explore immue escape in primary to metastatic breast cancer transition

Author(s):  
C Fremd ◽  
N Halama ◽  
R Wirtz ◽  
I Zoernig ◽  
H-P Sinn ◽  
...  
2010 ◽  
Author(s):  
Jacob E. Shabason ◽  
Tamalee Scott ◽  
Shuping Zhao ◽  
Uma T. Shankavaram ◽  
Philip J. Tofilon ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11095-11095
Author(s):  
M. M. Reinholz ◽  
K. A. Kitzmann ◽  
T. J. Hobday ◽  
D. W. Northfelt ◽  
B. LaPlant ◽  
...  

11095 Background: Biologic characterization of CTCs is increasingly important in determining metastatic breast cancer (MBC) patient (pt) prognosis and treatment prediction. Combined preliminary results from two earlier metastatic BC NCCTG trials, N0234 & N0336, suggested that the change in CTC mammaglobin (MGB1) gene expression between baseline and two cycles of chemotherapy predicted tumor response (p=0.04). The objectives of this study were to 1) determine CTC gene expression of CK19 and MGB1 before, during, and after treatment in N0436 & N0437 and 2) determine associations between baseline and post-treatment gene expression and treatment response. Methods: CTCs were enriched using CD45-depletion from ∼10ml EDTA blood obtained from metastatic BC pts before, after two cycles, and at end of treatment with either first/second-line irinotecan plus cetuximab (N0436) or first-line paclitaxel poliglumex and capecitabine (N0437). CK19 and MGB1 mRNA levels were determined using quantitative RT-PCR in baseline and serial CTC samples of up to 19 pts from N0436 and 40 pts from N0437. The relative gene expressions were normalized to β2-microglobulin and calibrated to healthy blood using the 2-ΔΔCt algorithm; a value of 2 was defined as positive for the respective marker. Results: CK19+ mRNA was detected in 58% of baseline samples from N0436 (11/19) and N0437 (23/40). MGB1+ mRNA was detected in 32% (6/19) and 38% (15/40) of N0436 and N0437 baseline samples, respectively. CK19+ mRNA was detected in 50% (7/14) and 56% (29/52) of N0436 and N0437 serial CTC samples, respectively. MGB1+ mRNA was detected in 29% (4/14) and 27% (14/52) of N0436 and N0437 serial CTC samples, respectively. Of the 66 serial samples, 27% of samples (18/66) had turned positive from baseline for CK19 or MGB1. CK19 mRNA was detected in 85% (33/39) of MGB1+ mRNA samples but their baseline mRNA levels were not correlated. Conclusions: CK19 mRNA was detected in MBC pts with similar frequencies to the CellSearch imaging system. CK19 was detected at a higher frequency than MGB1. In the majority of cases, MGB1 was co-expressed with CK19. Associations between gene expression and treatment response using Chi-Squared analyses and Cox regression models will be presented. No significant financial relationships to disclose.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22090-e22090
Author(s):  
Claudette Falato ◽  
Nicholas Tobin ◽  
Julie Lorent ◽  
Linda Sofie Lindström ◽  
Jonas C. S. Bergh ◽  
...  

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22071-e22071
Author(s):  
Manuel Sureda ◽  
Joseba Rebollo ◽  
Elena Ma Martínez ◽  
Francisco J. Fernández-Morejón ◽  
Vicente Munoz ◽  
...  

2005 ◽  
Vol 11 (17) ◽  
pp. 6226-6232 ◽  
Author(s):  
Sherry X. Yang ◽  
Richard M. Simon ◽  
Antoinette R. Tan ◽  
Diana Nguyen ◽  
Sandra M. Swain

2017 ◽  
Vol 63 (10) ◽  
pp. 1585-1593 ◽  
Author(s):  
Maren Bredemeier ◽  
Philippos Edimiris ◽  
Pawel Mach ◽  
Mikael Kubista ◽  
Robert Sjöback ◽  
...  

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.


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