Evaluation of risk recurrence in early breast cancer assessed by Oncotype DX and tumor cell dissemination to blood and bone marrow.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11516-e11516
Author(s):  
Bahriye Aktas ◽  
Agnes Bankfalvi ◽  
Martin Leonhard Heubner ◽  
Rainer Kimmig ◽  
Sabine Kasimir-Bauer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Statistical Analysis ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Data Set ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Genomic Test

e11516 Background: The OncotypeDX assay is a validated genomic test that predicts the likelihood of breast cancer (BC) recurrence, patients’ (pts) survival within 10 years of diagnosis and benefit of chemotherapy in early-stage, N0, ER-pos BC. In addition, disseminated tumor cells (DTC) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood, especially stemness like tumor cells (slCTCs) including cells being able to perform epithelial-mesenchymal transition (EMT), have been associated with worse outcome in BC. Here we use OncotypeDX as well as the presence of DTCs, CTCs and slCTCs to evaluate the risk for recurrence in early BC pts. Methods: In total, 90 pts with newly diagnosed HER2-neg early stage BC received breast conserving surgery and sentinel lymphonodectomy. 17 pts were ER-/PR-, 12 pts ER+/PR-, 3 pts ER-/PR+ and 59 pts were ER+/PR+. Analysis of OncotypeDX and KI67 were performed. In case of G2 tumors, UPA and PAI1 were determined as further proliferation markers in tissue samples. Two BM aspirates from these patients were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. Furthermore, 2 x5 ml blood were analyzed for CTCs with the AdnaTest BreastCancer for the detection of EpCAM, MUC-1, HER-2, and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for the presence of slCTCs using the AdnaTest EMT (multiplex RT-PCR for TWIST, AKT2, PI3K), and the AdnaTest TumorStemCell (ALDH1). Results: OncotypeDX was performed in 68/91 cases. 30/68 pts (44%) had a low RS, 29/68 pts (43%) an intermediate RS and 9/68 pts (13%) a high RS, respectively. BM aspiration could be performed in 70/91 pts with a positivity rate of 34% (24/70) for DTCs. CTCs were detected in 16/68 (25%) evaluable pts and slCTCs in 27/62 (44%) pts, respectively. In preliminary statistical analysis, KI67, PR and grading are showing association to RS as well as the presence of slCTCs. Tissue samples of patients with G2 tumors (N=65) underwent evaluation for UPA/PAI1analysis. Conclusions: Final statistical analysis for the complete data set including correlations to RS with all evaluable parameter will be available for presentation at the ASCO.

scholarly journals CIRCULATING TUMOR CELLS: CLINICAL SIGNIFICANCE IN BREAST CANCER (REVIEW)

2017 ◽  
Vol 72 (6) ◽  
pp. 450-457 ◽  
Author(s):  
E. V. Kaigorodova
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Significance ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Clinical Importance ◽  
Metastatic Breast ◽  
Mesenchymal Transition

Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor participants in the EMT. There is increasing interest in the study of the molecular biological characteristics of CTCs. Many researchers consider circulating tumor cells (CTC) as one of the variants of «liquid biopsy in real time». In this review, we discuss the clinical significance of CTCs in breast cancer and in particular the prognostic and predictive significance both in early stage and metastatic breast cancer, as well as the pathogenetic role of CTCs in venous thromboembolism. Evaluation of various characteristics of CTCs is promising for the study of new biomarkers and targets for targeted therapies. The clinical importance involves the determination of the heterogeneity of the CТC and in particular of the stem subpopulation of these cells, cells with signs of EMТ, with no evidence of stem cells, and with a combination of these features.

Detection and prevalence of disseminated tumor cells from the bone marrow of early stage male breast cancer patients

2015 ◽  
Vol 152 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Andreas D. Hartkopf ◽  
Florin-Andrei Taran ◽  
Christina B. Walter ◽  
Markus Hahn ◽  
Tanja Fehm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Male Breast Cancer ◽  
Early Stage ◽  
Disseminated Tumor Cells ◽  
Male Breast ◽  
Breast Cancer Patients

Sunitinib as adjuvant therapy for women with early-stage breast cancer and disseminated tumor cells in bone marrow.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1094-1094
Author(s):  
J. Li ◽  
M. E. Melisko ◽  
P. N. Munster ◽  
M. Pelayo ◽  
M. M. Moasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Adjuvant Therapy ◽  
Tumor Cells ◽  
Early Stage ◽  
Disseminated Tumor Cells ◽  
Early Stage Breast Cancer

Treg and Teff in the bone marrow of early-stage breast cancer patients with disseminated tumor cells.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e21049-e21049
Author(s):  
D. G. Wolf ◽  
D. Fong ◽  
L. Scherrer ◽  
A. Wolf ◽  
D. Reimer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Early Stage ◽  
Disseminated Tumor Cells ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients

Classifying circulating, mutation bearing tumor cells from breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 580-580
Author(s):  
William Strauss ◽  
Paul W. Dempsey ◽  
Jessamine Winer-Jones ◽  
Catherine Bingham ◽  
R. Katherine Alpaugh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Molecular Analysis ◽  
New Technologies ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Patients ◽  
Disease Heterogeneity ◽  
Mesenchymal Transition ◽  
Tissue Biopsy

580 Background: The treatment of advanced breast cancer demands systemic therapies that can address disease heterogeneity and the development of treatment resistance without a “real-time” molecular window into disease biology. New technologies have focused on increased capture and molecular analysis of circulating tumor cells (CTCs) including cells undergoing epithelial mesenchymal transition (EMT). We conducted a pilot experiment to test the efficiency of capture and cytokeratin (CK) detection and the presence of single point variants (SNV) to determine the best utility of scoring alternatives for CTC. Methods: EpCAM expressing CTC were recovered from breast cancer patients using CellSearch (Veridex) and LiquidBiopsy (Cynvenio Biosystems). EpCAM recovery and CK scoring were indexed in spiked samples and in 12 inflammatory breast cancer (IBC) patient samples using antibodies against CKs 7, 8 or CKs 1-8, 10, 13-16, 18, 19. Additionally, LiquidBiopsy template was analyzed using an Ampliseq 1.0 panel on the IonTorrent PGM. SNV present in the CTC but not white blood cell (WBC) negative controls were identified and where possible, compared to tissue biopsy SNV analyzed using Foundation One (Foundation Medicine). Results: CTCs were detected using CellSearch 10/12 (83%) (range 0-2502 CTC/7.5ml) and LiquidBiopsy 12/12 (100%) (range 6-2800 CTC/7.5mL). More CK positive events were scored using CKs 1-8, 10, 13-16, 18, 19 than CKs 7, 8 in patient samples. Upon sequencing, shared germline polymorphisms were observed in CTC and WBC. Conversely, 1 or 2 SNV were detected in the Epcam selected population but not WBC controls from 6/12 patients (frequency 1.1%-2.1% with 520-5160x coverage) with SNV observed in TP53, MPL, PIK3ca, MET and IDH1. All but one of the PIK3ca mutations were absent in evaluable tissue biopsy. Conclusions: CTC recovery and scoring are two separate events. Altered CK detection emphasized the need to tailor CTC classification to specific disease settings. Sequence analysis showed one correlated SNV among 6 evaluable comparisons to tissue reflecting variable analysis as well as the biologic disparity of metastatic disease. This pilot demonstrates the feasibility of using CTC for molecular analysis.

scholarly journals Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice

2017 ◽  
Vol 114 (43) ◽  
pp. 11494-11499 ◽  
Author(s):  
Yixiang Xu ◽  
Dong-Kee Lee ◽  
Zhen Feng ◽  
Yan Xu ◽  
Wen Bu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Migration And Invasion ◽  
Small Subset ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Twist1 is an epithelial–mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent. Twist1 expression was detected in ∼6% of the advanced WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT-inducing TFs (Snail, Slug, Zeb2), lost ERα and luminal marker K8, acquired basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E-cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely diminished the expression of the aforementioned EMT-inducing TFs and basal and mesenchymal markers, but maintained the expression of the luminal markers. Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs coexpressed Twist1 with other EMT-inducing TFs and both epithelial and mesenchymal markers. Mice with advanced WT tumors developed extensive lung metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal marker expression. Mice with advanced Twist1TKO tumors developed very little lung metastasis. Therefore, Twist1 is required for the expression of other EMT-inducing TFs in a small subset of tumor cells. Together, they induce partial EMT, basal-like tumor progression, intravasation, and metastasis.

scholarly journals Involvement of immune system and Epithelial–Mesenchymal-Transition in increased invasiveness of clustered circulatory tumor cells in breast cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Samane Khoshbakht ◽  
Sadegh Azimzadeh Jamalkandi ◽  
Ali Masudi-Nejad
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Cells ◽  
Distant Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Rank Test ◽  
Support Vector ◽  
Mesenchymal Transition ◽  
Menstrual Cycles

Abstract Background Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches. Methods Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan–Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection. Results Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients’ metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs. Conclusions In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.

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