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

SIMPLE SUMMARY: Breast cancer is the most prevalent type of cancer worldwide. By late 2020, there were 7.8 million women alive who had been diagnosed with breast cancer during the previous 5 years. HER2 overexpression in breast cancer is associated with poor prognosis. Existing HER2-targeting therapies significantly improved patient outcomes; still, designing these personalized treatments relies on accurate and comprehensive assessment of HER2 alterations. Frequent HER2 status determination during disease monitoring can be performed using circulating tumour cells (CTCs). Using a novel microfluidic device, we isolated and enumerated CTCs from metastatic breast cancer patients and assessed their HER2 expression in a comparative study with the current gold standard technology. CTCs isolated with our microfluidic technology showed to be a valuable biomarker, and their phenotypical analysis hinted utility to discriminate patient populations, although further validation is needed. ABSTRACT: 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 RUBYchip(TM) 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 RUBYchip(TM) 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.