Abstract P6-10-11: In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients

Abstract

Background: Chemoresistance in cancer cells is the underlying reason for treatment failure. Real-time monitoring of chemoresistance and response (CRR) is a fundamental but unmet prerequisite of precision oncology. Repetitive invasive biopsies to obtain tumor tissue for in-vitro CRR profiling are neither feasible nor advisable. Circulating Tumor Associated Cells (C-TACs) have been proposed for functional assessment of CRR. In this observational study, we performed CRR profiling on viable C-TACs from breast cancer patients.

Methods: In this 3 arm study, viable C-TACs were harvested from 15 ml of peripheral blood obtained from 242 breast cancer patients using CellWizard™, an epigenetically active media with paradoxical cytotoxicity that selectively kills normal cells and simultaneously confers survival benefit on cells of tumorigenic origin. C-TACs were stained with EPCAM, CK, CD45 and GCDFP. Viable Tumor Derived Cells (TDCs) harvested from freshly biopsied tumor tissue (Arm 1, N=48) and concurrently obtained C-TACs were simultaneously CRR profiled irrespective of whether patient was pre-treated or otherwise. Arm 2 (N=100) included refractory (pre-treated) patients where C-TACs were evaluated for resistance to previously administered drugs. Arm 3 (N=124) included recently diagnosed therapy naïve patients where C-TACs were evaluated for innate chemoresistance.

Results: In Arm 1, CRR profile of C-TACs showed 96.1% concordance with CRR profile of concurrently obtained TDCs. In Arm2, CRR profiling of C-TACs identified chemoresistance due to prior drug exposure in 91.4% of patients. In Arm 3, innate chemoresistance was observed in 42% of patient samples towards commonly used first / second line Standard of Care drugs belonging to various functional categories such as mitotic inhibitors, DNA damaging agents, topo inhibitors and antimetabolites.

Conclusion: This study shows for the first time the feasibility of CRR profiling of C-TACs and its correlation to in-vitro and in-vivo CRR characteristics of the tumor. Adoption of C-TAC based CRR profiling can provide unprecedented real time treatment oversight towards treatment selection and monitoring of drug resistance for personalized treatment of breast cancer patients.

Citation Format: Timothy Crook, Dadasaheb Akolkar, Sanket Patil, Vishakha Mhase, Revati Patil, Cynthe Sims, Vineet Datta, Sachin Apurwa, Viwek Mane, Ashok Gawai, Madhavi Apastamb, Ajay Srinivasan, Rajan Datar. In vitro chemo interrogation of viable circulating tumor associated cells from breast cancer patients [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 P6-10-11.