OBJECTIVES: Circulating Tumor Cell (CTC) enumeration is a liquid biopsy testing approach for which the peer-reviewed evidence base has grown rapidly in recent years, especially in metastatic breast cancer for which an FDA-cleared assay exists. In the current research, we aimed to assess publicly-available, peer-reviewed evidence for clinical utility of CTC testing in patients with metastatic breast cancer (MBC).

METHODS: A comprehensive search in PubMed was conducted investigating use of the FDA-cleared CellSearch® CTC assay in MBC. More than 130 peer-reviewed publications from 2004-2022 were reviewed for utility along with any published follow-on studies.

RESULTS: Evidence for the significance of CTCs in MBC staging and prognosis was confirmed in numerous published studies; one analysis on pooled data from 1,944 patients across 17 European centers indicated that CTC levels and changes in CTC levels during the course of treatment had greater prognostic utility than standard serum tumor markers (Bidard, Lancet Oncol 2014). Another pooled analysis of 2,436 patients with MBC suggested CTC enumeration can stratify Stage IV disease irrespective of standard clinical and molecular factors, e.g. disease site and subtype (Cristofanilli, Crit Rev Hem Oncol 2019). Moreover, multiple studies demonstrated utility in monitoring changes in disease status and at least six included comparisons of CTCs to radiographic imaging for identifying early changes in disease status and response to therapy. In some cases, detectable changes in CTCs preceded imaging detection by ≥2 months (Liu, JCO 2009). One multicenter RCT (n=755) showed that CTC-guided therapy significantly improved survival outcomes (Bidard, JAMA Oncol 2021).

CONCLUSIONS: The peer-reviewed clinical literature confirms the clinical utility of CTC enumeration in MBC for disease stratification and monitoring, treatment selection and response prediction, with implications for CTCs to be applied in routine clinical practice as a tool for treatment decisions and more efficient allocation of healthcare resources/ cost reduction.