Cancer panel analysis of circulating tumor cells in patients with breast cancer

Lee, Cham Han; Lee, Soo Jeong; Choi, Sung Ho; Son, Byung Ho; Lee, Jong Won; Yu, Jong Han; Kwon, Nak‐Jung; Lee, Woo Chung; Yang, Kap‐Seok; Lee, Dong Hyoung; Han, Du Yeol; Choi, Mi So; Park, Pyeong‐Soo; Lee, Hyun Kyung; Kim, Myoung Shin; Lee, Jinseon; Jeon, Byung Hee

doi:10.3892/ol.2018.8646

Cited by 8 publications

(9 citation statements)

References 25 publications

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“…CTC isolation was performed using a SMART BIOPSY SYSTEM Isolation kit (cat no. CIKW10; Cytogen, Inc., Seoul, Korea) 61 , 66 , 67 . Briefly, blood samples were incubated with 20 µg/µl of antibody cocktail (complex) from the SMART BIOPSY SYSTEM Isolation kit (Cytogen, Inc.) targets white blood cells (CD45) and red blood cells (globin), captures epithelial CTCs, which was uniquely developed by Cytogen Inc., for 20 min and were then mixed with pre-activation buffer followed by density gradient centrifugation at 400 × g for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…CTC circulating tumor cell, HR hormone receptor, LN lymph node, NCT neoadjuvant chemotherapy, pCR pathologic complete response, RFS relapse-free survival, OS overall patient survival. https://doi.org/10.1038/s41598-020-74577-w www.nature.com/scientificreports/ All of the patients with hormone receptor-positive tumors subsequently received adjuvant tamoxifen or aromatase inhibitors after surgery.Circulating tumor cell detection-blood collection and CTC enrichment.A volume of 5 cc of blood was collected from each patient into Acid Citrate Dextrose tubes (BD Vacutainer; BD Biosciences, San Jose, CA, USA) and the samples were processed within four hours to minimize cell loss and processing failure47,[66][67][68] .…”

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confidence: 99%

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Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Gwark

Kim

Kwon

et al. 2020

Sci Rep

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We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80–63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26–155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Gwark

Kim

Kwon

et al. 2020

Sci Rep

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“…Targeted NGS analysis on genomic DNA, extracted from patients’ white blood cells (WBC), was performed to exclude all germline sequence variants during the evaluation of mutational results, as previously described 32,33 . As shown in Supplementary Tables, we found several discrepancies at both intra-patient and inter-patient levels and, although in few instances we found shared gene variants in primary tumors matched with CTC samples (e.g.…”

Section: Resultsmentioning

confidence: 99%

“…Several Authors also described such heterogeneity at single-CTC level 26,29,33–35,44 , but the minimal amount of DNA extracted from a single cell requires preliminary WGA for downstream molecular analyses. WGA is a time-consuming procedure that may provide technical errors such as inadequate coverage, allelic dropouts, false negative and false positive results 23,38 that may affect the analytical quality of NGS procedures 18,38 .…”

Section: Discussionmentioning

confidence: 99%

Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer

D’Oronzo

Lovero

Palmirotta

et al. 2019

Sci Rep

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Enumeration of circulating tumor cells (CTCs) may reflect the metastatic potential of breast cancer (BC). By using the DEPArray, we investigated CTCs with respect to their epithelial-to-mesenchymal transition phenotype and compared their genomic heterogeneity with tissue biopsies. Seventeen stage IV BC patients were enrolled. Pre-enriched CTC suspensions were stained with fluorescent-labeled antibodies to epithelial (E) and mesenchymal (M) markers. CTC samples were processed by DEPArray system and clustered in relation to their markers. DNA from CTCs, as well as from primary tumor samples, was sequenced by next generation sequencing to assess the mutational state of 50 major cancer-related genes. We identified four different CTC subsets that harbored different gene variants. The most heterogenous CTC subsets included the M+/E− phenotype, which, however, expressed only 7 repeatedly mutated genes, while in the M−/E+ subset multiple mutations affected only 2 out of 50 genes. When matching all gene variants among CTC subsets, a small number of mutations was shared by only 4 genes, namely ATM, FGFR3, PIK3CA, and TP53 that, however, were absent in primary tumors. Our results postulate that the detected mutations in all CTC subsets may be considered as genomic markers of metastatic dissemination to be investigated during early stages of BC.

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“…Even with aggressive surgery or chemoradiation therapy, microscopic cancer cells can remain. Recent work on circulating cancer cells has provided evidence of the presence of numerous microscopic cancer cells after local treatment (4). Therefore, removal of these remaining cancer cells is important for complete cure of such malignancies, a process in which host immunity plays an important role.…”

Section: Introductionmentioning

confidence: 99%

Accelerated elimination of human cancer cells by a CD40 agonist antibody combined with a PD‑1 antagonist in CD4‑depleted mice

et al. 2019

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The elimination of residual microscopic cancer cells is important cancer treatment. The immunoediting theory describes the balance between the immune system and cancer cells. The current study investigated changes in the immune system during the elimination of cancer cells and evaluated the influence of cluster of differentiation (CD)4 or CD8 depletion. A human squamous cell cancer cell line (SNU1041) was injected in the lateral tongue of immunocompetent mice and the changes in the CD4, CD8, CD11b, CD19, CD40 and CD40 ligand (L) populations in the blood, lymph nodes and spleen were evaluated using flow cytometry, and changes in serum cytokine levels were evaluated using a magnetic bead panel. Cancer cell elimination was delayed by CD4 depletion but not by CD8 depletion. The CD8-depleted group indicated increased levels of CD40L, interferon-gamma, interleukin (IL)-10, IL-6, and tumor necrosis factor-α. It was concluded that CD4 served a crucial role in the elimination of human cancer cells. Furthermore, the efficacies of CD40 agonist and programmed cell death protein 1 (PD1) antagonist treatments were assessed in CD4-depleted mice. CD40 agonist treatment resulted in faster cancer cell elimination and increased cytokine excretion. In conclusion, CD4 or CD40L significantly influenced cancer elimination. CD40 agonist antibodies may be potent adjuvant agents that can be used in patients with reduced CD4 or CD40L expression.

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Cancer panel analysis of circulating tumor cells in patients with breast cancer

Cited by 8 publications

References 25 publications

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer

Accelerated elimination of human cancer cells by a CD40 agonist antibody combined with a PD‑1 antagonist in CD4‑depleted mice

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