Comparison of predictive mutations in circulating tumor cells and matched tissue biopsies from metastatic breast cancer patients

Objective Targeted therapy has become the preferred approach to treat most cancers, including metastatic breast cancer. However, the predictive utility of the primary tumor is limited and obtaining serial biopsies of metastatic lesions is challenging. Therefore, using liquid biopsies, which can act as a dynamic diagnostic tool, is an appealing concept.

Here, we performed a comparative mutation analysis of tissue biopsies and circulating tumor cells (CTCs) yielded from blood.

Material & methods DNA from the most recent tissue biopsies available of 27 metastatic breast cancer patients was extracted. CTCs were enriched with the CellSearch system and were isolated by micromanipulation. Clinically relevant mutation in PIK3CA, ESR1, AKT1, and ERBB2 were identified by next generation sequencing.

Results CTCs were detected in 18 samples and sequencing results were obtained for CTCs of 15 patients. CTC analysis failed in 3 cases due to DNA degradation and low quantity of the CTCs. Predictive mutations were detected in tissue of 10 patients. If CTC positive, similar mutations were found in CTCs in all cases. Moreover, in CTCs from 5 patients, further predictive mutations in PIK3CA, ESR1, or AKT1 were identified that could not be detected in tissue.

Conclusion The analysis of CTCs offers the opportunity to detect predictive information that could not be gained from tissue biopsies but may be of clinical relevance. Therefore, liquid biopsies should be considered as a powerful tool that complements tissue analysis to optimize targeted therapy selection.

Publication History

Article published online:
21 June 2022