Circulating Tumor Cells in Early Breast Cancer

Thery, Laura; Meddis, Alessandra; Cabel, Luc; Proudhon, Charlotte; Latouche, Aurélien; Pierga, Jean‐Yves; Bidard, François-Clément

doi:10.1093/jncics/pkz026

Cited by 80 publications

(60 citation statements)

References 64 publications

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“…However, we were not able to demonstrate that epithelial CTCs, EMT-CTCs, or CSC-CTCs serve as surrogate markers for pCR. In agreement, ancillary studies of the phase III GeparQuattro and Neo ALTTO trials were not able to confirm an association either; a decrease in the CTC count after neoadjuvant treatment in locally advanced breast cancer was not significantly associated with better response to systemic treatment [27][28][29]. In a more recent meta-analysis of 2090 patients treated with neoadjuvant chemotherapy, CTC detection-before neoadjuvant chemotherapy or before surgery-by CellSearch was also not able to demonstrate a correlation between CTC numbers and pCR [30].…”

Section: Discussionmentioning

confidence: 97%

EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

Fujii

Kida

et al. 2020

PLoS ONE

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Background Tumor cells with a mesenchymal phenotype and/or cancer stem-like cells (CSCs) are known to contribute to metastasis and drug resistance. Circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) and CTCs reflecting a dedifferentiated CSC phenotype may not be detected using only an anti-EpCAM antibody to capture them. We used an antibody-independent CTC enrichment platform, ApoStream ® , which does not rely on any antibody, including anti-EpCAM, to capture EMT-and CSC-CTCs in breast cancer patients who received neoadjuvant chemotherapy and correlated them to pathological complete response (pCR). Methods Blood samples from newly diagnosed breast cancer patients were prospectively collected before neoadjuvant chemotherapy (T 0), after chemotherapy but before surgery (T 1), and after surgery (T 2) and processed using ApoStream. CTCs detected were stained with additional markers to define 3 CTC subsets with the following phenotypes: epithelial CTCs (CK +, EpCAM+ or E-cadherin+), EMT-CTCs (β-catenin+ or vimentin+), and CSC-CTCs (CD44 + and CD24 low). Results We enrolled 55 patients, 47 of which had data for analysis.

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Section: Discussionmentioning

confidence: 97%

EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

Fujii

Kida

et al. 2020

PLoS ONE

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“…Prognostic significance of CTCs was also clearly demonstrated in adjuvant setting [78]. The randomized trial SUCCESS-A on more than 2000 patients revealed that CTC positivity before as well as after adjuvant chemotherapy was an independent prognostic factor, with poor disease-free survival (DFS) (hazard ratio (HR) = 2.28, 95% CI = 1.48 to 3.50) and OS (HR = 3.95, 95% CI = 2.13 to 7.32).…”

Section: Early Breast Cancer; Prognostic Value Programs and Trialsmentioning

confidence: 92%

“…The small number of CTCs per ml of peripheral blood is the major challenging physical limit. CTCs are particularly rare in non-metastatic breast cancer, usually less than 1 CTC/10 mL of blood is found [78], with five or more CTCs being a rare event (1-5.9%) [79]. CTCs are detectable in about 20% to 25% of patients with localized nonmetastatic breast cancer at the time of diagnosis using a lower threshold (≥1 CTC per 7.5 mL blood) than in MBC (≥ 5 CTC per 7.5 mL blood) [79][80][81][82].…”

Section: Early Breast Cancer; Prognostic Value Programs and Trialsmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

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Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.There are two main hypotheses describing cancer dissemination: linear progression, according to which, metastatic potential is gained gradually, and the whole process proceeds in steps and needs time, and parallel progression, according to which dissemination takes place early on, even before clinical manifestation of the tumor [6,7] (Figure 1). In the linear progression model, the evolving primary tumor gives rise to metastases due to increasingly aggressive and invasive phenotypes of the subclones of tumor cells. This model is in agreement with the postulated role of the epithelial-to-mesenchymal transition (EMT) in cancer and assumes active degradation of the stroma and migration into blood vessels by the motile, invasive single cells that broke loose from the epithelial monolayer. In contrast to that, parallel progression postulates intravasation by passive shedding, which may take place shortly after the angiogenic switch, occurring during the early, pre-invasive stage of tumor development [8,9].

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“…Our results demonstrated that CTCs were present even in stage 0 or I melanoma. Although CTCs are present in limited numbers [9], they exist even in the early stages of melanoma, as well as in other diseases such as breast and lung cancer [18][19][20] Primary tumors with minimal invasion may exert their metastatic potential via releasing CTCs.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Monitoring Circulating Tumor Cells as a Therapeutic Biomarker in Melanoma with BRAF Mutation

Okuyama

Kiniwa

Nakamura

et al. 2020

Preprint

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Background: Circulating tumor cells (CTCs) are non-invasive biomarkers that could be used to characterize changes in tumors. In this study, we monitored the number of CTCs, as well as the BRAF genotype of individual CTCs. Methods: CTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). Results: Examination of patients with stage 0–III melanoma detected CTCs even in patients with early disease (stage 0 or I). Next, we analyzed CTCs in five patients with stage IV melanoma during treatment with BRAF/MEK inhibitors. The number of CTCs fluctuated in association with the drug response in four of the five patients, suggesting that the total number of CTCs usually reflected the drug response. Interestingly, one of those patients had CTCs with seven different BRAF genotypes, and the mutated CTCs disappeared upon treatment with BRAF/MEK inhibitors, except for those harboring BRAFA598V.Conclusions: CTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect drug response during treatment with BRAF/MEK inhibitors. Furthermore, genetic heterogeneity of BRAF may contribute to drug resistance of BRAF/MEK inhibitor. Our findings demonstrate the usefulness of CTC analysis in melanoma for monitoring targeted therapies and understanding mechanism of drug resistance.

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Circulating Tumor Cells in Early Breast Cancer

Cited by 80 publications

References 64 publications

EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Usefulness of Monitoring Circulating Tumor Cells as a Therapeutic Biomarker in Melanoma with BRAF Mutation

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