HER2-targeted therapy influences CTC status in metastatic breast cancer

Abstract

Purpose As an independent, negative-prognostic biomarker for progression-free survival (PFS) and overall survival (OS), circulating tumor cells (CTCs) constitute a promising component for developing a liquid biopsy for patients with metastatic breast cancer (MBC). The effects of HER2-targeted therapy such as trastuzumab, pertuzumab, T-DM1, and lapatinib on CTC status and longitudinal enumeration were assessed in this trial. Methods CTC status of 264 patients with MBC was analyzed prior to and after 4 weeks of a new line of palliative systemic therapy. CTCs were assessed using CellSearch®. Three groups were compared: patients with HER2-positive MBC receiving ongoing HER2-targeted therapy (n = 28), patients with de novo HER2-positive MBC and no HER2-targeted therapy in the last 12 months prior to enrollment and start of HER2-targeted therapy (n = 15), and patients with HER2-nonamplified disease and no HER2-targeted therapy (n = 212). Results Positive CTC status (≥ 5 CTC/7.5 ml blood) at enrollment was observed in the 3 groups for 17.9, 46.7, and 46.2% (p = 0.02) of patients, respectively. At least one CTC/7.5 ml was seen in 28.6, 53.3, and 67.0% (p < 0.001) of these patients. Furthermore, 3.6, 40.0, and 3.3% (p < 0.001) of the patients had at least one HER2-positive CTC. After 4 weeks of therapy 7.1, 0.0, and 31.1% (p = 0.001) of patients had still a positive CTC status (≥ 5 CTC/7.5 ml blood). At least one CTC/7.5 ml was still observed in 25.0, 20.0, and 50.5% (p = 0.004) of the patients. Furthermore, 7.1, 0.0, and 1.9% (p = 0.187) had at least one HER2-positive CTC. After 3 months of therapy, 35.7, 20.0, and 28.3% (p = 0.536) showed disease progression. Conclusions HER2-targeted therapy seems to reduce the overall CTC count in patients with MBC. This should be taken into account when CTC status is used as an indicator for aggressive or indolent metastatic tumor disease.

Quantitative Approach for Protein Analysis in Small Cell Ensembles by an Integrated Microfluidic Chip with MALDI Mass Spectrometry

“…One example for quantitative differences in protein amounts relates to circulating tumor cell (CTC) analysis. It was reported that studying Her2 and EpCAM expression in CTCs could guide personalized anticancer therapy. , In addition, protein post-translational modifications (PTMs) occur during or after protein biosynthesis that dramatically alter the functionality of proteins. Investigation of the imbalance in protein PTMs is particularly important for various diseases such as cancers, diabetes, and neurodegenerative disorders .…”

HER2 Phenotyping of CTCs By Peptide-Functionalized Nanoparticles As The Diagnostic Biomarkers of Anti-HER2 Treatment in Breast Cancer

“…Second, in a small sample size with second blood draws (n = 14), we showed the dynamic change of CTC enumeration and CTC-HER2 phenotypes after the combination therapy. As expected, the depletion of epithelial CTCs was far from a practical predictive biomarker of the treatment outcomes [61]. A few groups investigated the clinical significances of evolutionary HER2 status on CTCs.…”

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

“…Since our results show that the number of HER2+ cells decreased between times of collection in patients under anti-HER2 targeted therapy, it may suggest a positive response to therapy. The higher number of CTCs in total by one of the patients (patient 1) may be indicative that the tumour burden is still high, but tumour phenotypical characteristics have changed, ideally even to a less invasive and more well managed subtype [88,89]. The presence of HER2+ cells, isolated by the RUBYchip™, in patients that were not diagnosed as having HER2+ tumours by the tissue biopsy analysis was observed.…”