Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer

Schott, Dorothea; Pizon, Monika; Pachmann, Ulrich; Pachmann, Katharina; Schobert, Rainer; Wittig, Andrea; Mäurer, Matthias

doi:10.1016/j.tranon.2021.101009

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…The CellSearch system which used EpCAM antibody labeled magnetic beads to enrich CTCs, has disadvantages such as low sensitivity, inability to capture live cells and conduct subsequent genetic testing and medication guidance, requirement of large blood samples, and high detection cost. The TUMORFISHER technology developed by the National Center for Nanoscience of the Chinese Academy of Sciences uses magnetic nanobeads labeled with polypeptides which specifically recognize EpCAM to efficiently isolate CTCs in peripheral blood, and the captured CTCs are active enough for subsequent molecular biological analysis ( 20 , 25 ).Our findings showed that the prevalence of CTCs detected by the CellSearch system was 30.0% (15/50) before neoadjuvant therapy in patients with HER-2 EBC, which is similar to the results reported in previous studies ( 9 – 12 ). On the other hand, the baseline CTC checkout rate of the TUMORFISHER system was 54.0% (27/50), which was significantly higher than that of the CellSearch system (p=0.008).…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, dynamic changes of CTCs have a role in predicting treatment efficacy (4)(5)(6)(7)(8). The checkout rate of CTC in patients with early breast cancer (EBC) is significantly lower than that of MBC, ranging from 21.5% to 24% as reported in previous study, and≥ 1 CTC/7.5ml blood is a poor prognostic factor for disease free survival (DFS) and OS (9)(10)(11)(12). However, the relationship between CTC counts before neoadjuvant therapy and pathologic complete response (pCR) rate is still uncertain (13).The pCR status of patients with HER-2-positive EBC after neoadjuvant therapy has a definite prognostic value and can guide preoperative and postoperative treatment to further improve patients' survival, so the guidelines currently recommend neoadjuvant therapy as the first choice for patients with breast tumors ≥ 2 cm or axillary lymph node metastasis (14)(15)(16).…”

Section: Introductionmentioning

confidence: 97%

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An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer

Zhou

Hao

et al. 2022

Front. Oncol.

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BackgroundNeoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain.MethodsThe study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy.ResultsThe sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods.ConclusionsOur study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 97%

An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer

Zhou

Hao

et al. 2022

Front. Oncol.

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“…Cancer stem cells (CSCs) are the source of primary and metastatic tumors, as well as the basis of chemo-and radioresistance, which leads to tumor recurrence (61). Studies have shown that CSCs often reappear after chemotherapy and express the ATP binding cassette subfamily B member 5 (ABCB5) protein, which mediates multidrug resistance in multiple cancers.…”

Section: Regulation Of Neoplastic Growth and Metastasismentioning

confidence: 99%

Exosomes: A New Pathway for Cancer Drug Resistance

Zhong

et al. 2021

Front. Oncol.

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Exosomes are extracellular vesicles (EVs) that are secreted into body fluids by multiple cell types and are enriched in bioactive molecules, although their exact contents depend on the cells of origin. Studies have shown that exosomes in the tumor microenvironment affect tumor growth, metastasis and drug resistance by mediating intercellular communication and the transport of specific molecules, although their exact mechanisms of action need to be investigated further. In this review, we have summarized current knowledge on the relationship between tumor drug resistance and exosomes, and have discussed the potential applications of exosomes as diagnostic biomarkers and therapeutic targets.

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“…This particularly underlines the activation of TLR4 and COX-2 observed in this study, suggesting that increased cytokine and chemokine production suppresses an adaptive immune response and promotes metastatic processes [ 76 , 77 ]. It is also possible that the detected CETC are radio-resistant tumor stem cells or subclones with pronounced differentiation potential, which can survive treatment (especially if such cells circulating with the blood stream do not receive the total radiation dose applied locally to the breast/chest wall) and lead to a selected subpopulation of CETC with increased malignant potential [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. The strong activation of NANOG in all patients seems to support this hypothesis [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

“…Endocrine therapy might influence changes in the numbers of CETCs as well as gene expression as a confounding factor [ 87 ]. This and other confounders cannot be eliminated as patients were treated according to current guidelines.…”

Section: Discussionmentioning

confidence: 99%

Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients

et al. 2021

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Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC from whole blood samples of patients with early-stage breast cancer before and after radiotherapy (RT) using the maintrac® method was investigated. Single-cell expression analyses were performed with qRT-PCR on a panel of selected genes: GAPDH, EpCAM, NANOG, Bcl-2, TLR 4, COX-2, PIK3CA, Her-2/neu, Vimentin, c-Met, Ki-67. In all patients, viable CETC were detected prior to and at the end of radiotherapy. In 7 of the 9 (77.8%) subjects examined, the CETC number at the end of the radiotherapy series was higher than before. The majority of genes analyzed showed increased expression after completion of radiotherapy compared to baseline. Procedures and methods used in this pilot study proved to be feasible. The method is suitable for further investigation of the underlying molecular biological mechanisms occurring in cells surviving radiotherapy and possibly the development of radiation resistance.

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Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer

Cited by 10 publications

References 46 publications

An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer

An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer

Exosomes: A New Pathway for Cancer Drug Resistance

Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients

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