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      A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival

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          Abstract

          Background

          Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts.

          Methods

          Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0–2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information.

          Results

          536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350–0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269–0.887).

          Conclusions

          Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

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          Most cited references30

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          Circulating tumor cells, disease progression, and survival in metastatic breast cancer.

          We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P 18 months, P 18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer. Copyright 2004 Massachusetts Medical Society
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            Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500.

            Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS). Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2). Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P < .001). This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy. © 2014 by American Society of Clinical Oncology.
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              Circulating tumor cells: biology and clinical significance

              Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                03 April 2024
                15 April 2024
                03 April 2024
                : 10
                : 7
                : e29217
                Affiliations
                [a ]Department of Breast Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, People's Republic of China
                [b ]Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, 100850, People's Republic of China
                Author notes
                []Corresponding author. Department of Breast Oncology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 East Street, Beijing, 100071, People's Republic of China. lijianbin@ 123456csco.org.cn
                [∗∗ ]Corresponding author. Department of Breast Oncology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 East Street, Beijing, 100071, People’s Republic of China. jiangzefei@ 123456csco.org.cn
                [1]

                Contributed equally.

                Article
                S2405-8440(24)05248-4 e29217
                10.1016/j.heliyon.2024.e29217
                11016733
                38623216
                ea0306fb-9050-454a-9af7-8b258a228f39
                © 2024 The Authors. Published by Elsevier Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 23 October 2023
                : 2 April 2024
                : 2 April 2024
                Categories
                Research Article

                circulating tumor cells,breast cancer,overall survival,counting,cellsearch,cellcolloector

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