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

Abstract

Breast cancer (BC) is a disease characterized by high degrees of heterogeneity at morphologic, genomic, and genetic levels, even within the same tumor mass or among patients. As a consequence, different subpopulations coexist and less represented clones may have a selective advantage, significantly influencing the outcome of BC patients. Circulating tumor cells (CTCs) represent a rare population of cells with a crucial role in metastatic cascade, and in recent years have represented a fascinating alternative to overcome the heterogeneity issue as a “liquid biopsy”. However, besides the raw enumeration of these cells in advanced epithelial tumors, there are no CTC-based assays applied in the clinical practice to improve personalized medicine. In this review, we report the latest findings in the field of CTCs for intra-tumoral heterogeneity unmasking in BC, supporting the need to deepen their analysis to investigate their role in metastatic process and include the molecular characterization in the clinical practice. In the future, CTCs will be helpful in monitoring patients during treatment, as well as to better address therapeutic strategies.

Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer

“…Tools for stratifying patients and defining the real benefit of escalated treatments are needed to reduce unnecessary overtreatment and maximize the therapeutic effect. However, it is common to observe different transitional phenotypes and molecular heterogeneity derived from the epithelial to mesenchymal transition of CTCs in the bloodstream, limiting their applicability in clinical practice [76]. The molecular heterogeneity of CTCs may be more representative of the entire clones of metastatic BC, which is notoriously a heterogenous disease but is also present in the earlier stages [77].…”

Tumor-Promoting Properties of TMEM9A in Breast Cancer Progression <i>via</i> Activating the Wnt/β-Catenin Signaling Pathway

“…3) According to the report, 20-30% of BC patients may undergo metastasis after tumor resection and adjuvant therapy of the primary tumor. 4) Although researchers have made great strides in the treatment and diagnosis of BC, 5,6) BC is still a major health issue and currently represents a top biomedical research priority.…”

Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients

“…Further, recent evidence suggests the feasibility for a CTC-driven treatment choice ( 12 ). To note, CellSearch is limited to EpCAM-positive cells, and several studies showed how downregulation of EpCAM and epithelial-mesenchymal transition occur often in cancer and might reduce detection rate ( 11 ). Indeed, several groups have reported about the presence of non-epithelial CTC and their correlation with worse prognosis and resistance to therapies ( 9 ).…”

“…Indeed, several groups have reported about the presence of non-epithelial CTC and their correlation with worse prognosis and resistance to therapies ( 9 ). For this major drawback, new technologies for CTC enrichment and enumeration are under development, as for example size-based methods, which however are limited by a low specificity ( 11 ). Besides their clinical significance, CTCs isolation and characterization offer the opportunity for probing the biological evolution of cancer towards the metastatic stage ( 7 ).…”