scholarly journals Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1005 ◽  
Author(s):  
Giulia Brisotto ◽  
Eva Biscontin ◽  
Elisabetta Rossi ◽  
Michela Bulfoni ◽  
Aigars Piruska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Label Free ◽  
Breast Cancer Patients ◽  
Combining Data ◽  
Definition Of

Circulating tumor cells (CTCs) belong to a heterogeneous pool of rare cells, and a unequivocal phenotypic definition of CTC is lacking. Here, we present a definition of metabolically-altered CTC (MBA-CTCs) as CD45-negative cells with an increased extracellular acidification rate, detected with a single-cell droplet microfluidic technique. We tested the prognostic value of MBA-CTCs in 31 metastatic breast cancer patients before starting a new systemic therapy (T0) and 3–4 weeks after (T1), comparing results with a parallel FDA-approved CellSearch (CS) approach. An increased level of MBA-CTCs was associated with: i) a shorter median PFS pre-therapy (123 days vs. 306; p < 0.0001) and during therapy (139 vs. 266 days; p = 0.0009); ii) a worse OS pre-therapy (p = 0.0003, 82% survival vs. 20%) and during therapy (p = 0.0301, 67% survival vs. 38%); iii) good agreement with therapy response (kappa = 0.685). The trend of MBA-CTCs over time (combining data at T0 and T1) added information with respect to separate evaluation of T0 and T1. The combined results of the two assays (MBA and CS) increased stratification accuracy, while correlation between MBA and CS was not significant, suggesting that the two assays are detecting different CTC subsets. In conclusion, this study suggests that MBA allows detection of both EpCAM-negative and EpCAM-positive, viable and label-free CTCs, which provide clinical information apparently equivalent and complementary to CS. A further validation of proposed method and cut-offs is needed in a larger, separate study.

scholarly journals Dysmetabolic circulating tumor cells are prognostic in metastatic breast cancer

2019 ◽  
Author(s):  
Giulia Brisotto ◽  
Eva Biscontin ◽  
Elisabetta Rossi ◽  
Michela Bulfoni ◽  
Aigars Piruska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Value ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Prognostic Information ◽  
Definition Of ◽  
Over Time

ABSTRACTThe prognostic value of the circulating tumor cells (CTCs), defined as EpCAM+, Cytokeratin (8, 18, 19)+ and CD45-nucleated cells, has been provided in metastatic breast cancer (mBC), with Level I of evidence. However, CTCs belong to a heterogeneous pool of rare cells, and there isn’t consensus on an univocal definition of CTCs. Here, we present a definition of metabolically altered CTCs (MBA-CTC) as CD45-negative cells with an increased extracellular acidification rate (iECAR), supported by the presence of iECAR among the hallmarks of cancer. We tested the prognostic value of MBA-CTC present in mBC patients before starting a new systemic therapy (T0) and 3-4 weeks after (T1). Samples were analyzed in parallel with CellSearch platform (CS). Standard RECIST criteria were used to determine patients’ responses to treatment.In our cohort of n=31 mBC patients, a level of MBA-CTCs above the cut-off was associated with: i) a shorter median PFS both pre-therapy (123 days vs 306; p<0.0001) and during therapy (139 vs 266 days; p= 0.0009); ii) a worse OS both pre-therapy (p=0.0003, 82% survival vs 20%) and during therapy (p=0.0301, 67% survival vs 38%); iii) good agreement with therapy response (kappa=0.685). Both the trend of MBA-CTCs over time and the combined results of the two assays (MBA and CS) enabled more accurate stratification. MBA and CS results showed fair (K=0.33) and poor (K=0.077) agreement at T0 and T1, respectively. This fact and the increased accuracy in combining results suggest that the assays detect different CTC subsets. In conclusion, MBA-CTCs does provide prognostic information at least equivalent to CS, and are even more informative when analyzed over time or combined with CS-CTCs.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

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