Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer

Jauch, Sarah F.; Sprick, Martin R.; Schütz, Florian; Schönfisch, Birgitt; Brucker, Sara Y.; Deutsch, Thomas M.; Nees, Juliane; Saini, Massimo; Becker, Lisa; Burwinkel, Barbara; Sinn, Hans‐Peter; Marmé, Frederik; Pantel, Klaus; Jäger, Dirk; Sohn, Christof; Trumpp, Andreas; Wallwiener, Markus; Schneeweiß, Andreas

doi:10.1007/s10549-018-4972-y

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…One can hypothesize that at a later stage, the predictive value of CTM is less powerful than at earliest stages. In this case, as previously reported for CTCs , a variation between time points might be more informative (42,43).…”

Section: Discussionsupporting

confidence: 61%

Identification of atypical circulating tumor cells with prognostic value in metastatic breast cancer patients

Lopresti

Boudin

Finetti

et al. 2020

Preprint

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Purpose: Circulating tumor cells (CTCs) have a tremendous potential for diagnosis and treatment of breast cancer patients. Here, we performed a unique analysis of all atypical circulating cells isolated with a filtration-based technology from metastatic breast cancer (mBC) patients. Patients and methods: The PERMED-01 study enrolled patients with mBC, refractory to systemic therapy, and with an accessible lesion to biopsy. We analyzed atypical circulating cells isolated from patients' blood at the time of inclusion using Screencell® Cyto device. For 23 out of 91 analyzed patients, this was completed by advanced immunofluorescence staining of atypical circulating cells. Subsets cut-offs were established using a two-component Gaussian finite Mixture Model, and evaluated for correlation with clinico-pathological data, including progression-free survival (PFS) and overall survival (OS). Results: Three subsets of atypical circulating cells, absent from controls (n=7), were observed in cancer patients (n=91): isolated (iCTCs), Clusters (CTM), and Giant CTCs (gCTCs). CTCs' median number was 8.33 per mL. Co-expression of stem and drug resistance markers was associated with intermediate epithelial to mesenchymal transition phenotype in CTM and gCTCs, but not in iCTCs. Presence of gCTC was associated with shorter PFS and OS. Concerning PFS, assigning an immunofluorescence-based Epithelial to Mesenchymal status improved their prognostic value. Conclusion: This study brings to light the diversity of CTCs in mBC patients and their specific molecular profiles regarding epithelial to mesenchymal transition, stemness and drug resistance status. It also highlights the involvement of an atypical circulating cell subset, the gCTCs, as a prognostic factor for PFS and OS.

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Section: Discussionsupporting

confidence: 61%

Identification of atypical circulating tumor cells with prognostic value in metastatic breast cancer patients

Lopresti

Boudin

Finetti

et al. 2020

Preprint

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“…Regarding the optimized aCTC cut-off, >50% reduction (n = <50% reduction (n = 49) showed a median PFS of 6 (5-10) vs. 3 (3-5) months (p = 0.0085) and a OS of 24 (17-34) vs. 10 (7-16) months (p < 0.0001). Regarding the optimized iCTC+aCTC >66.7% reduction (n = 57) vs. <66.7% reduction (n = 51) showed a median PFS of 6 (5-10) vs. months (p = 0.0063) and a median OS of 24 [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] vs. 10 (7-15) months (p = 0.0025). The impact of the optimized cut-offs on OS and PFS is shown in Figure 3.…”

Section: Resultsmentioning

confidence: 99%

“…The prognostic value of baseline CTC counts and kinetics of CTC number (CTC kinetics) in relation to systemic therapy has been demonstrated in recent studies [6,10,24]. Thus far, either a change in CTC status or a 25% reduction or increase as a cut-off point has been used to define a significant change in CTC counts, rendering them useful for studying the influence of CTC kinetics on breast cancer prognosis [6,7,13,24,25].…”

Section: Introductionmentioning

confidence: 99%

Cut-Off Analysis of CTC Change under Systemic Therapy for Defining Early Therapy Response in Metastatic Breast Cancer

Deutsch

Feißt

et al. 2020

Cancers

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Detection of circulating tumor cells (CTC) can distinguish between aggressive and indolent metastatic disease in breast cancer patients and is thus considered an independent, negative prognostic factor. A clear decline in CTCs is observed in patients who respond to systemic therapy. Nevertheless, CTCs can decrease in patients experiencing disease progression during systemic therapy, too. This study aims to determine the differences between CTC decline in patients responding to therapy and those in whom disease is progressing. Therefore, CTC values were compared at the start and after one cycle of a new line of systemic therapy. In all, 108 initially CTC-positive patients (with ≥5 intact CTCs in 7.5 mL blood) were enrolled in this study and intact and apoptotic CTCs were measured via the CellSearch® system. A cut-off analysis was performed using Youden’s J statistics to differentiate between CTC change in the two groups. Here, 64 (59.3%) patients showed stable disease or partial response vs. 44 (40.7%) presenting disease progression. Median overall survival was 23 (range: 4–92) vs. 7 (2–43) months (p < 0.001). Median intact CTC count at enrollment was 15.0 (5–2760) vs. 30.5 (5–200000) cells (p = 0.39) and 2.5 (0–420) vs. 8.5 (0–15000) cells after one cycle of systemic therapy (p = 0.001). Median apoptotic CTC count at enrollment was 10.5 (0–1500) vs. 9 (0–800) cells (p = 0.475) and 1 (0–200) vs. 3 (0–250) cells after one cycle of systemic therapy (p = 0.01). A 50% reduction in baseline apoptotic CTC count represents the optimal cut-off to differentiate between therapy response and disease progression. An apoptotic CTC reduction of ≤10% is 74% specific for early disease progression.

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“…Considering the limitations of antibody-based CTC capture technology, it is not possible to capture CTCs lacking the EpCAM protein or CTCs that have undergone the epithelial-mesenchymal transition and other CTCs such as high EGFR. [21][22][23][24] In this study, EGFR peptides with a higher affinity were used to modify magnetic spheres to isolate EGFR phenotype CTCs and detect EGFR gene mutations in these isolated CTCs. A new CTC analysis method based on EGFR peptides was developed.…”

Section: Discussionmentioning

confidence: 99%

“…The CTC capturing method of the CellSearch system is based on EpCAM antibody‐coated magnetic nanoparticles. Considering the limitations of antibody‐based CTC capture technology, it is not possible to capture CTCs lacking the EpCAM protein or CTCs that have undergone the epithelial‐mesenchymal transition and other CTCs such as high EGFR 21–24 …”

Section: Discussionmentioning

confidence: 99%

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

Wang

Zhang

et al. 2020

Thoracic Cancer

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Background: This study aimed to identify an efficient, simple, and specific method of detecting mutations in the epidermal growth factor receptor (EGFR) gene in isolated lung cancer circulating tumor cells (CTCs) and to improve the ability to obtain tumor tissue clinically. Methods: EGFR peptide lipid magnetic spheres (EG-P-LMB) were prepared by reverse evaporation, and characterization and cell capture efficiency assessed. The peripheral blood samples of 30 lung cancer patients were isolated and identified with the EG-P-LMB using 20 healthy volunteers as controls. Finally, the isolated CTCs were tested for EGFR gene mutations, and the tissue samples selected for comparison. Results: The prepared magnetic spheres had a smaller particle size and higher stability according to the particle size potential test. Their morphology was homogeneous by atomic force observation, and the UV test showed that there were peptides on the surface. The separation efficiency of EG-P-LMB was greater than 90% in PBS and greater than 80% in the blood simulation system. Compared with the tissue sample results, the positive rate of EGFR gene mutations was 94%. The CTC test results of 27 patients were consistent with the tissue test results of the corresponding patients, and the consistency with the tissue comparison test results was 90% (27/30). Conclusions: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice.

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Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer

Cited by 11 publications

References 42 publications

Identification of atypical circulating tumor cells with prognostic value in metastatic breast cancer patients

Identification of atypical circulating tumor cells with prognostic value in metastatic breast cancer patients

Cut-Off Analysis of CTC Change under Systemic Therapy for Defining Early Therapy Response in Metastatic Breast Cancer

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres

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