Abstract
Simple SummaryLiquid biopsy appears as a feasible opportunity to complement tissue biopsy within breast cancer research and real-time monitoring of the disease. In this review, we not only summaries cur-rent trends in the study of CTCs as a potential biomarker of response to systemic therapies but also the technical challenges for their implementation in clinical practice, including the role of free circulating DNA and new approaches based on the isolation of CTCs from body fluids. We also highlight the importance of a consensus on the standardization of liquid biopsy methodologies as a fundamental requirement for their implementation in clinical practice.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.
Highlights
The modern procedure of liquid biopsy has been a breakthrough in clinical oncology and has an extraordinary potential as a tool for breast cancer (BC) screening and diagnosis, to estimate prognosis, and both to select targeted-treatments and monitor response
The different layers of information provided by liquid biopsy (CTCs, cell-free tumor DNA (ctDNA), exosomes) in patients with cancer would help us to better understand tumor biology and evolution
Hopefully contribute to advance from prognosis to prediction, this is the real challenge in the era of the so-called precision oncology, being able to identify biomarkers that guide us through the challenging process of deciding which is the most appropriate treatment in each particular moment of each patient’s BC evolution
Summary
Extracellular vesicles appear as a potential source of tumoral biomarkers since they are in fluids circulation and their isolation and analysis seems to be feasible to be implemented in early cancer detection Both exosomes and other vesicles have been studied by their relevant role in cell signaling and tumoral microenvironment. They have been widely discussed in recent literature highlighting their value to determine the tissue of origin, to monitor response and resistances to treatments and adapt therapy to the specific needs of an individual patient, or to detect minimal residual disease [11,12]. The biopsy of metastatic tissue is sometimes not clinically possible due to its location (lung) complicating the correctly determination of the molecular profile of a tumor by the limitation of taking biopsies from different tumor sites [22]
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