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Identification of Atypical Circulating Tumor Cells with Prognostic Value in Metastatic Breast Cancer Patients
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International audience. Background: Circulating tumor cells (CTCs) have a strong potential as a quasi-non-invasive tool to set up precision medicine strategy for cancer patients. Tremendous efforts have been made to develop the second-generation of “filtration-based” technologies to detect CTCs, revealing a surprising heterogeneity among those cells. Here, we performed the largest and simultaneous analysis of all atypical circulating tumor cells (aCTCs) detected with a filtration-based technology, in a cohort of metastatic breast cancer (mBC) patients, and correlated their presence with clinicopathological and survival data. Methods: The PERMED-01 study enrolled patients with mBC refractory to systemic therapy. We prospectively analyzed aCTCs present at the time of inclusion in the study, using the Screencell®Cyto device (n=91). Subsets cut-offs were established and evaluated for correlation with clinicopathological data, including progression-free survival (PFS) and overall survival (OS). Results: The median number of aCTCs found in mBC was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in mBC patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter PFS and OS in multivariate analyses. For 23 cases, the analysis was completed with advanced immunofluorescence staining and showed that CTM and g-aCTCs displayed a hybrid phenotype for epithelial and mesenchymal markers. Conclusions: This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels when using a Screencell®Cyto device. It reveals the gaCTC subset as a prognostic factor and a potential stratification tool that might help to orientate late-stage mBC patients’ therapeutic care.
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