A proof-of-concept study for the clinical utility of a circulating tumor cell-based mutation analysis

Background Over the last decades targeted therapy has become the preferred approach to treat breast cancer. However, the predictive utility of the primary tumor is limited and obtaining serial biopsies of metastatic lesions is challenging. Thus, the idea of deriving information about the tumor from liquid biopsies e.g. circulating tumor cells (CTCs) became popular.

Here, we present detailed data of a longitudinal proof-of-concept study of an index patient suffering from metastasized breast cancer over a time period of three years with the aim to understand the clinical utility of CTCs.

Methods The CTC count during several treatment regimens was regularly determined by CellSearch analyses. Mutations and chromosomal aberrations were analyzed by whole exome sequencing und array comparative genome hybridization during each treatment period.

Results A correlation between the CTC counts and the patient’s clinical situation was observed. Mutation analyses enabled to retrace the evolution of the tumor and could explain resistance mechanisms acquired during therapy. We hypothesized the AKT1 E17K mutation to be the driver of the metastatic process. When the tumor did not respond to paclitaxel treatment our findings were used to select everolimus to target the Akt1 pathway. During this liquid biopsy based treatment, CTC number detected by CellSearch dropped by 97.3 %. The observations on CTC numbers associated with the imaging of the metastatic burden.

Conclusion Our results underline the advantage of a liquid biopsy analysis to develop personalized therapies in the future. Analysis of such index cases can promote to further fathom the clinical utility of CTCs.

 

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Publication History

Article published online:
07 October 2020