Profiling of Invasive Breast Carcinoma Circulating Tumour Cells—Are We Ready for the ‘Liquid’ Revolution?

Abstract

As dissemination through blood and lymph is the critical step of the metastatic cascade, circulating tumour cells (CTCs) have attracted wide attention as a potential surrogate marker to monitor progression into metastatic disease and response to therapy. In patients with invasive breast carcinoma (IBC), CTCs are being considered nowadays as a valid counterpart for the assessment of known prognostic and predictive factors. Molecular characterization of CTCs using protein detection, genomic and transcriptomic panels allows to depict IBC biology. Such molecular profiling of circulating cells with increased metastatic abilities appears to be essential, especially after tumour resection, as well as in advanced disseminated disease, when information crucial for identification of therapeutic targets becomes unobtainable from the primary site. If CTCs are truly representative of primary tumours and metastases, characterization of the molecular profile of this easily accessible ‘biopsy’ might be of prime importance for clinical practice in IBC patients. This review summarizes available data on feasibility and documented benefits of monitoring of essential IBC biological features in CTCs, with special reference to multifactorial proteomic, genomic, and transcriptomic panels of known prognostic or predictive value.

Functional Genomic Analysis of Breast Cancer Metastasis: Implications for Diagnosis and Therapy

“…Analyzing CTCs as the link between the primary tumor and metastatic sites, therefore, would give insights into the biology of the metastatic cascade. Moreover, it may serve as a valid counterpart for the assessment of prognostic and predictive factors in patients with metastatic BC (MBC) [79]. The process of tumor cells invading the basement membrane and surrounding tissue and entering the bloodstream is a first and crucial step for metastasis.…”

Circulating Tumor Cells as a Tool to Untangle the Breast Cancer Heterogeneity Issue

“…Indeed, after their detachment from the primary epithelial tumor, CTCs pass through vessel endothelium to enter body circulation. The entire metastatic process remains poorly efficient, since in the bloodstream CTCs present a short half-time (approximatively between one to three hours), with only 0.1% of cells surviving after 24 hours and 0.01% having a real metastatic potential [ 42 , 43 ]. Indeed, in the bloodstream, CTCs are susceptible to mechanical and environmental processes, such as oxidative stress, immune system, lack of growth factors, anoikis , and trauma due to the blood flow stress [ 44 ].…”

Challenges and achievements of liquid biopsy technologies employed in early breast cancer

“…CTCs can travel as individual cells through the bloodstream but it was recently discovered that they can also associate in clusters, which increases 23À50 times their metastatic capacity [43]. CTCs half-life is established in between one to three hours, with only 01% surviving for more than 24 h in the bloodstream, and 001% having the ability to metastasize [44,45]. CTCs are substantially less abundant in the blood of patients with early tumours, however there is evidence in the literature about the detection of CTCs in all breast cancer stages and their correlation with unfavourable prognosis, lack of treatment efficacy and tumour progression [46,47].…”

“…CTCs can travel as individual cells through the bloodstream but it was recently discovered that they can also associate in clusters, which increases 23–50 times their metastatic capacity [43] . CTCs half-life is established in between one to three hours, with only 0•1% surviving for more than 24 h in the bloodstream, and 0•01% having the ability to metastasize [ 44 , 45 ].…”