Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer
Open Access
- 19 April 2020
- Vol. 12 (4), 1005
- https://doi.org/10.3390/cancers12041005
Abstract
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.Funding Information
- European Research Council (269051, 640955)
- Associazione Italiana per la Ricerca sul Cancro (CUP:G23C17000800007 ID 20443)
- Nvidia (TITAN X)
This publication has 46 references indexed in Scilit:
- Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methodsInternational Journal of Cancer, 2018
- Integrating liquid biopsies into the management of cancerNature Reviews Clinical Oncology, 2017
- Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate CancerJAMA Oncology, 2016
- Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary TumorNeoplasia, 2016
- Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid BiopsyCancer Discovery, 2016
- AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate CancerThe New England Journal of Medicine, 2014
- Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient dataThe Lancet Oncology, 2014
- The Identification and Characterization of Breast Cancer CTCs Competent for Brain MetastasisScience Translational Medicine, 2013
- High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patientsAnnals of Oncology, 2012
- HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trialBreast Cancer Research and Treatment, 2010