Case Report: Analysis of Circulating Tumor Cells in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient

Abstract

Circulating tumor cells (CTCs) are a rare population of cells found in the bloodstream and represent key players in the metastatic cascade. Their analysis has proved to provide further core information concerning the tumor. Herein, we aim at investigating CTCs isolated from a 32-year-old patient diagnosed with triple negative spindle-shaped metaplastic breast cancer (MpBC), a rare tumor poorly responsive to therapies and with a dismal prognosis. The molecular analysis performed on the primary tumor failed to underline effective actionable targets to address the therapeutic strategy. Besides the presence of round-shaped CTCs, cells with a spindle shape were present as well, and through molecular analysis, we confirmed their malignant nature. This aspect was coherent with the primary tumor histology, proving that CTCs are released regardless of their morphology. Copy number aberration (CNA) profiling and variant analysis using next-generation sequencing (NGS) showed that these cells did not harbor the alterations exhibited by the primary tumor (PIK3CA G1049A mutation, MYC copy number gain). However, despite the great heterogeneity observed, the amplification of regions involved in metastasis emerged (8q24.22–8q24.23). Our findings support the investigation of CTCs to identify alterations that could have a role in the metastatic process. To the best of our knowledge, this is the first examination of CTCs in an MpBC patient.

Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis

“…In our study, testing single CTCs for a panel of 60 cancer-relevant genes revealed a great intra-patient degree of variant heterogeneity, supporting the existence of distinct self-specific mutational signatures for each CTC. Our study is not the first to describe the detection of mutational heterogeneity in single CTCs from MBC patients [ 11 , 57 , 58 , 59 , 60 ].…”

From phenotypical investigation to RNA-sequencing for gene expression analysis: A workflow for single and pooled rare cells

“…However, despite the emerging technologies in CTC detection and isolation, this operation Frontiers in Genetics frontiersin.org remains challenging. One of the most prominent approaches for CTC detection and recovery consists in the DEPArray technology, which proved to be a high-performance ally for the identification and recovery of CTCs and other rare cells by the expression of specific markers (Rossi et al, 2020;Rossi et al,. 2021b;Gallerani et al, 2021;Rossi et al,.…”

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

“…However, patients did not experience tumor progression, suggesting that CTCs did not have short-term metastatic potential, as a confirmation that CTC behavior could be different. Moreover, the first investigation of CTCs of a rare and aggressive subtype, metaplastic spindle-shaped BC, revealed that besides the high CTC count (>200 CTCs in 7.5 mL blood), great degrees of heterogeneity were present at both molecular and phenotypic levels, inferring that molecular characterization of CTCs could have a role in understanding the mechanisms underlying the metastatic process [ 77 ].…”