Encyclopedic tumor analysis guided personalized treatments for advanced refractory breast cancer

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Background Standard of Care systemic regimens have limited efficacy in advanced refractory breast cancers and offer diminishing benefits with each subsequent line. We hypothesized that integrative molecular and cellular investigations (‘Encyclopedic Tumor Analysis’, ETA) can reveal unexplored vulnerabilities in refractory breast cancer which can be effectively targeted using label- and organ-agnostic combinations of cytotoxic, targeted and endocrine agents. We report the findings from a cohort of patients with advanced refractory breast cancer who received ETA-guided personalized treatments. Methods Fresh tumor tissue was obtained from 27 patients and used for ETA, including molecular profiling (gene alterations + gene expression), immunohistochemistry, and in vitro chemoresistance and Response profiling of viable tumor derived cells against a panel of approved anti-tumor agents. MP, IHC and CRR datasets were integrated to generate patient specific drug priority lists with projected efficacy and safety. Patients received individualized combination regimens, and treatment response was evaluated by FDG PET-CT scans to determine Disease Control Rate (DCR) and Progression Free Survival (PFS). Results Among the 27 patients who received ETA-guided treatments, PR was observed in 16 patients and 9 patients showed SD (DCR = 96.3 %). Median PFS was 115 days. No significant therapy related adverse events (AEs) were noted - there were no grade IV AEs or treatment related deaths. Most patients reported stable to improved Quality of Life (QoL) in terms of disease-related symptoms and functional status. Conclusion ETA-guided treatments offered meaningful ORR and PFS benefits in this heavily pretreated population of advanced refractory breast cancers. Publication History Article published online: 16 July 2020 © Georg Thieme Verlag KG Stuttgart · New York

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