Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity

Functional studies giving insight into the biology of circulating tumor cells ( CTC s) remain scarce due to the low frequency of CTC s and lack of appropriate models. Here, we describe the characterization of a novel CTC ‐derived breast cancer cell line, designated CTC ‐ ITB ‐01, established from a patient with metastatic estrogen receptor‐positive ( ER + ) breast cancer, resistant to endocrine therapy. CTC ‐ ITB ‐01 remained ER + in culture, and copy number alteration ( CNA ) profiling showed high concordance between CTC ‐ ITB ‐01 and CTC s originally present in the patient with cancer at the time point of blood draw. RNA ‐sequencing data indicate that CTC ‐ ITB ‐01 has a predominantly epithelial expression signature. Primary tumor and metastasis formation in an intraductal PDX mouse model mirrored the clinical progression of ER + breast cancer. Downstream ER signaling was constitutively active in CTC ‐ ITB ‐01 independent of ligand availability, and the CDK 4/6 inhibitor Palbociclib strongly inhibited CTC ‐ ITB ‐01 growth. Thus, we established a functional model that opens a new avenue to study CTC biology.