An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer

Abstract

BackgroundNeoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain.MethodsThe study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy.ResultsThe sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods.ConclusionsOur study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients

“…With the development of detection techniques, novel methods such as microgels and antifouling nanofilm could facilitate in the separation and purification of CTCs, which could promote the CTCs to enter the clinic ( 66 – 68 ). Although the utility of CTC detection was not included in the clinical practice guidelines of BC, many studies have shown its great potential in the management of BC patients ( 69 , 70 ). For instance, the results obtained from Chakraborty’s group encouraged the incorporation of CTC quantification as a prognostic marker and for minimally invasive tumor burden assessment in multiple myeloma ( 71 ).…”

HER2 status of CTCs by peptide-functionalized nanoparticles as the diagnostic biomarker of breast cancer and predicting the efficacy of anti-HER2 treatment

“…Previously, our group has developed an innovative epithelial cell adhesion molecule (EpCAM) recognition peptide-functionalized magnetic nanoparticles (Pep@MNPs) that can be used to efficiently capture rare epithelial CTCs in 2.0 ml whole blood from patients with various solid tumors ( Bai et al, 2014 ; Liu et al, 2017 ; Yue et al, 2018 ; Xu et al, 2019 ; Tan et al, 2021 ). Pep@MNPs has superior sensitivity (54%—69%) to CellSearch in breast cancer patients on account of smaller diameter and higher density of recognition peptides on the surface of magnetic nanoparticles ( Bai et al, 2014 ; Liu et al, 2017 ; Zhou et al, 2022 ). Lower producing cost of peptides in Pep@MNPs becomes another more attractive benefit in clinical application as compared to CellSearch .…”