Technical Challenges for CTC Implementation in Breast Cancer

Abstract

Breast cancer is the most common neoplasm in women worldwide. Tissue biopsy, currently the gold standard to obtain tumor molecular information, is invasive and might be affected by tumor heterogeneity rendering it incapable to portray the complete dynamic picture by the absence of specific genetic changes during the evolution of the disease. In contrast, liquid biopsy can provide unique opportunities for real-time monitoring of disease progression, treatment response and for studying tumor heterogeneity combining the information of DNA that tumors spread in the blood (circulating tumor DNA) with CTCs analysis. In this review, we analyze the technical and biological challenges for isolation and characterization of circulating tumor cells from breast cancer patients. Circulating tumor cell (CTC) enumeration value is included in numerous clinical studies due to the prognostic’s role of these cells. Despite this, there are so many questions pending to answer. How to manage lymphocytes background, how to distinguish the CTCs subtypes or how to work with frozen samples, are some of the issues that will discuss in this review. Based on our experience, we try to address these issues and other technical limitations that should be solved to optimize the standardization of protocols, sample extraction procedures, circulating-tumor material isolation (CTCs vs. ctDNA) and the very diverse methodologies employed, aiming to consolidate the use of CTCs in the clinic. Furthermore, we think that new approaches focusing on isolation CTCs in other body fluids such as cerebrospinal or ascitic fluid are necessary to increase the opportunities of circulating tumor cells in the practice clinic as well as to study the promising role of CTC clusters and their prognostic value in metastatic breast cancer.

Recent Advances in Methods for Circulating Tumor Cell Detection

“…However, new methods that exploit technological advances to detect CTCs in other body fluids are emerging. These approaches are important because of their potential to open up new sources of CTCs and advance research on CTC clusters in metastatic cancers [ 15 ]. In particular, malignant pleural and peritoneal effusions are a richer source of CTCs and CTC clusters than peripheral blood [ 16 , 17 ].…”

Biological Characterization and Clinical Relevance of Circulating Tumor Cells: Opening the Pandora’s Box of Multiple Myeloma

“…Herein, we summarize different studies characterizing CTCs from a phenotypic, genetic, and transcriptomic point of view in MM, as well as their clinical applicability. Many excellent reviews expanding this topic in other cancer types are available in this journal [23,24] and elsewhere [25][26][27].…”

Sequencing of cerebrospinal fluid in non‐small‐cell lung cancer patients with leptomeningeal metastasis: A systematic review

“…However, the difference in CSF was rarely discussed and needs further study. The current limitation in sequencing cells in CSF corresponds to technical defects, associated with low abundance of CTC in biofluids, inevitable damage to tumor cells during sample preparation, and additional complex assessment of bioinformatics analyses 31–33 . Therefore, if qualified cell samples in CSF are too scarce, cfDNA may be more suitable for patients with LM.…”