scholarly journals HER2 Expression in Circulating Tumour Cells Isolated from Metastatic Breast Cancer Patients Using a Size-Based Microfluidic Device

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4446
Author(s):  
Cláudia Lopes ◽  
Paulina Piairo ◽  
Alexandre Chícharo ◽  
Sara Abalde-Cela ◽  
Liliana R. Pires ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real Time ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
Tumour Cells ◽  
Circulating Tumour Cells ◽  
Breast Cancer Patients ◽  
Disease Evolution

HER2 is a prognostic and predictive biomarker in breast cancer, normally assessed in tumour biopsy and used to guide treatment choices. Circulating tumour cells (CTCs) escape the primary tumour and enter the bloodstream, exhibiting great metastatic potential and representing a real-time snapshot of the tumour burden. Liquid biopsy offers the unique opportunity for low invasive sampling in cancer patients and holds the potential to provide valuable information for the clinical management of cancer patients. This study assesses the performance of the RUBYchip™, a microfluidic system for CTC capture based on cell size and deformability, and compares it with the only FDA-approved technology for CTC enumeration, CellSearch®. After optimising device performance, 30 whole blood samples from metastatic breast cancer patients were processed with both technologies. The expression of HER2 was assessed in isolated CTCs and compared to tissue biopsy. Results show that the RUBYchipTM was able to isolate CTCs with higher efficiency than CellSearch®, up to 10 times more, averaging all samples. An accurate evaluation of different CTC subpopulations, including HER2+ CTCs, was provided. Liquid biopsy through the use of the RUBYchipTM in the clinic can overcome the limitations of histological testing and evaluate HER2 status in patients in real-time, helping to tailor treatment during disease evolution.

scholarly journals Liquid Biopsy: New Tool to Overcome CDKi Resistance Mechanism in Luminal Metastatic Breast Cancer

2021 ◽  
Author(s):  
Miriam González-Conde ◽  
Celso Yanez ◽  
Rafael López-López ◽  
Clotilde Costa
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Hormone Receptors ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

scholarly journals Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Amanda Bortolini Silveira ◽  
François-Clément Bidard ◽  
Marie-Laure Tanguy ◽  
Elodie Girard ◽  
Olivier Trédan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Simultaneous Detection ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Breast Cancer Patients ◽  
Targeted Next Generation Sequencing ◽  
Patient Prognosis

AbstractCirculating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.

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