Identification of Atypical Circulating Tumor Cells with Prognostic Value in Metastatic Breast Cancer Patients

Simple Summary In this study we have isolated and analyzed atypical cells found in the blood of metastatic breast cancer patients using a micro-filtration technic. This technic, being very easy to implement, was also extremely useful for studying circulating tumors cells' (CTCs) heterogeneity in cancer patients. We highlighted three subsets of CTCs, with different independent unfavorable prognostic values for progression-free and overall survival. We demonstrated that these cells can further be analyzed by immunofluorescence to narrow their molecular profiles and identify specific characteristics. Moreover, we identified a subset of CTCs, for which positivity might be a useful stratification tool to select patients more susceptible to benefit from early clinical trials testing novel therapeutics, which frequently enroll late-stage, already heavily pre-treated and thus poor-responder patients. Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation filtration-based technology to isolate CTCs, the Screencell (TM) technology (Sarcelles, France), we performed a large and simultaneous analysis of all atypical circulating tumor cells (aCTCs) isolated from the blood of metastatic breast cancer (mBC) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials.

Automated summary

In this study, atypical cells in the blood of metastatic breast cancer patients were isolated and analyzed using a micro-filtration technic. Three subsets of circulating tumor cells were identified, each with different prognostic values. Moreover, a subset of CTCs was found to be a potential stratification tool for selecting patients for early clinical trials. This study highlights the heterogeneity of CTCs and their potential as a non-invasive tool for precision medicine.