Analysis of Circulating Tumor Cells in Breast Cancer

Eroglu, Zeynep; Fielder, Odicie

doi:10.6004/jnccn.2013.0118

Cited by 27 publications

(30 citation statements)

References 54 publications

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“…In comparison to Adams et al, 11,12 our capture efficiency was slightly lower than what they reported but within reasonable expectations. A review by Eroglu et al, 13 summarizes eight CTC studies from patients with metastatic breast cancer where approximately 60% of patients had detectable CTCs using CellSearch, which also aligns our data to the common CTC capture values in breast cancer patients with metastatic disease.…”

Section: Methodssupporting

confidence: 81%

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Brechbuhl¹,

Vinod-Paul²,

Gillen

et al. 2020

Molecular Carcinogenesis

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For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single‐cell RNA‐sequencing (scRNA‐seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size‐exclusion membranes followed by scRNA‐seq of enriched CTCs and carry‐over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial–mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD‐1/PD‐L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA‐seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune‐evasive competence.

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Section: Methodssupporting

confidence: 81%

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Brechbuhl¹,

Vinod-Paul²,

Gillen

et al. 2020

Molecular Carcinogenesis

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“…In early stage BC patients (cancer stage I and II), our CTCs detection rate can reach 80.43% and 91.53%, respectively, which is also much higher than other studies concerning CTC detection in early stage BC patients. 9,24 Furthermore, CTCs were detected in three of six BC patients with carcinoma in situ, the very early stage of tumor. Taken together, our results suggest that CytoSorter ® CTCs capture system has a greater sensitivity to detect CTCs in BC and it might be used as a biomarker to assist in the screening and early diagnosis of BC.…”

Section: F I G U R E 2 Circulating Tumor Cellsmentioning

confidence: 97%

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer

et al. 2020

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Purpose In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). Methods A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter®, a microfluidic‐based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. Results Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1‐4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut‐off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. Conclusion Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.

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“…Previous CTC studies have mainly focused on the development of CTC enrichment technology (Hong and Zu 2013 ; Alix-Panabieres and Pantel 2014 ; Krebs et al 2014 ; van der Toom et al 2016 ), the correlation between CTC number and clinical prognosis (Arya et al 2013 ; Harouaka et al 2014 ; Alix-Panabieres and Pantel 2016 ), and biological processes driving cancer metastasis and recurrence (Hodgkinson et al 2014 ; Massague and Obenauf 2016 ). For example, scientists have discovered a correlation between CTC number and the prognosis of breast cancer (Eroglu et al 2013 ; Bidard et al 2016 ), colon cancer (Hardingham et al 2015 ), and prostate cancer (Hu et al 2013 ), whereby the CTC number can be used to assess cancer prognosis. Based on these principles, the US Food and Drug Administration (FDA) approved the CellSearch™ system as an aid for monitoring breast cancer (Cristofanilli NEJM 2004 ), prostate cancer (Cohen JCO 2008 ), and colon cancer (Scher Lancet Oncol 2009 ) progression.…”

Section: Introductionmentioning

confidence: 99%

Progress and challenges of sequencing and analyzing circulating tumor cells

et al. 2017

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Circulating tumor cells (CTCs) slough off primary tumor tissues and are swept away by the circulatory system. These CTCs can remain in circulation or colonize new sites, forming metastatic clones in distant organs. Recently, CTC analyses have been successfully used as effective clinical tools to monitor tumor progression and prognosis. With advances in next-generation sequencing (NGS) and single-cell sequencing (SCS) technologies, scientists can obtain the complete genome of a CTC and compare it with corresponding primary and metastatic tumors. CTC sequencing has been successfully applied to monitor genomic variations in metastatic and recurrent tumors, infer tumor evolution during treatment, and examine gene expression as well as the mechanism of the epithelial-mesenchymal transition. However, compared with cancer biopsy sequencing and circulating tumor DNA sequencing, the sequencing of CTC genomes and transcriptomes is more complex and technically difficult. Challenges include enriching pure tumor cells from a background of white blood cells, isolating and collecting cells without damaging or losing DNA and RNA, obtaining unbiased and even whole-genome and transcriptome amplification material, and accurately analyzing CTC sequencing data. Here, we review and summarize recent studies using NGS on CTCs. We mainly focus on CTC genome and transcriptome sequencing and the biological and potential clinical applications of these methodologies. Finally, we discuss challenges and future perspectives of CTC sequencing.

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Analysis of Circulating Tumor Cells in Breast Cancer

Cited by 27 publications

References 54 publications

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer

Progress and challenges of sequencing and analyzing circulating tumor cells

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Analysis of Circulating Tumor Cells in Breast Cancer

Cited by 27 publications

References 54 publications

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter® CTC capture system in patients with breast cancer

Progress and challenges of sequencing and analyzing circulating tumor cells

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Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer