Abstract P6-10-27: The clinical utility of mutations detected on circulating tumor cells: A proof of concept study based on a metastasized breast cancer index patient
Authors: Franken André , Behrens Bianca , Reinhardt Florian , Yang Liwen , Rivandi Mahdi , Cieslik Jan-Philipp , Dietzel Frederic , Stoecklein Nikolas H. , Niederacher Dieter , Fehm Tanja , Neubauer Hans 
Published: March 2020

Abstract
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 by analyzing e.g. circulating tumor cells (CTCs) became popular. CTCs are shed into the blood by tumor tissue and are commonly considered as precursor cells for metastasis formation. They are an independent prognostic indicator of progression free and overall survival and their predictive utility is currently investigated in several studies.
Here, we present detailed data of a longitudinal proof-of-concept study of a single 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. After treatment with aromatase inhibitors the CTCs harbored two activating ESR1 mutations and the AKT1 E17K mutation. The activating ESR1 mutations disappeared during following chemotherapy whereas the AKT1 E17K mutation remains present in the CTC ever since. Thus we hypothesized the AKT1 E17K mutation to be the driver of the metastatic process. When the tumor did not respond to paclitaxel treatment and the patient was suffering from further expanding metastases and strong adverse side effects 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.
Citation Format: André Franken, Bianca Behrens, Florian Reinhardt, Liwen Yang, Mahdi Rivandi, Jan-Philipp Cieslik, Frederic Dietzel, Nikolas H. Stoecklein, Dieter Niederacher, Tanja Fehm, Hans Neubauer. The clinical utility of mutations detected on circulating tumor cells: A proof of concept study based on a metastasized breast cancer index patient [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-27.