OBJECTIVES: Circulating Tumor Cell (CTC) enumeration is a liquid biopsy test for which the evidence base has grown rapidly, especially in metastatic breast cancer (MBC) for which an FDA-cleared assay exists, the CellSearch® (CS) CTC platform. This assay can also assess HER2 status. In this research, we aimed to assess publicly-available, peer-reviewed evidence for clinical utility of CTC testing and CTC HER2 assessment in MBC patients.

METHODS: A comprehensive search in PubMed was conducted investigating use of the CS® CTC assay and the added CTC HER2 assessment. More than 150 peer-reviewed publications from 2004-2023 were reviewed for utility along with any published follow-on studies.

RESULTS: Evidence for the significance of CTCs in MBC prognosis was confirmed in numerous studies; one analysis on pooled data (n=1,944) indicated that CTC levels at baseline and during the course of treatment had greater prognostic utility than standard serum tumor markers. Another pooled analysis (n=2,436) shows CTC enumeration can stratify Stage IV disease irrespective of standard clinical and molecular factors. Multicenter RCTs show that CTC-guided therapy significantly improved survival outcomes in 1^st line, and in 2^nd line, post CDK4/6 inh.

Over 10 studies provide results of CTC HER2 status adding information over HER2 assessment from the tumor sample; it is a strong prognostic parameter. Prospective trial data shows CTC HER2 status is predictive of response to HER2 targeted therapy.

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. The CTC HER2 assessment on the same assay may provide added prognostic and predictive utility over HER2 assessment of the primary tumor. CS CTC assay can be applied in routine clinical practice as a tool for treatment decisions and more efficient allocation of healthcare resources/ cost reduction, and for added HER2 assessment.