Many of the current approaches to personalized medicine rely on sequencing DNA to identify actionable mutations. However, growing evidence suggests that a multi-omic approach to more broadly assess biology is needed to improve patient outcomes. We have implemented a workflow for tissue acquisition, multi-omic clinical testing, and correlated computational biology analysis, within the Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Program (Mitri et al, J Transl Med 2018). We report biopsy metrics, CLIA analytics utilized, the operation of a multi-omics tumor board, and clinical outcomes in metastatic breast cancer patients. A detailed clinical history of each patient was obtained, including demographics, tumor type, treatment and response to prior therapies, imaging, and blood tumor biomarkers. A comprehensive set of clinical assays was performed on newly obtained tumor biopsies, including immunohistochemistry (ER, PR, HER2, AR, BCL-2, and PD-L1), a targeted next-generation sequencing panel covering 225 genes (GeneTrails® Comprehensive Solid Tumor Panel), whole exome sequencing (Tempus xE), whole transcriptomic sequencing (Illumina TruSeq RNA exome), and a multiplex protein analysis of 22 key cancer proteins and phosphoproteins on the Nanostring platform (NanoString Vantage 3D™ Solid Tumor Panel). The integrated clinical and analytical information was made available to the multidisciplinary SMMART Clinical Tumor Board that provided treatment recommendations; the final treatment plan was at the discretion of the treating physician. Between 1/1/2017-1/1/2020, 53 breast cancer patients were consented. Seven screen-failed due to a lack of sites amenable to biopsy and 8 were actively co-consented to other clinical trials. The remaining 38 patients are included in this preliminary report. A total of 63 biopsies were collected from lymph node, liver, bone, soft tissue, lung, skin, breast, and brain. Serial biopsies (≥2) were obtained for 15 patients. Analytics were generated in 93.7% of biopsies. Tumor boards were held for 15 patients (17 total sessions). The experience and information gathered thus far have yielded the following unique cases: (1) single patient analysis of omics, imaging, and response over 42 months, (2) identification of an ERBB3 mutation with downstream pathway activation that responded to HER2-targeted therapy, and (3) clinically significant variation in hormonal and HER2 receptor status over time. We will provide an analysis across the 38 patients of treatment outcomes, analytics information content, biological changes observed through serial biopsies, and tumor board interventions. We demonstrate the feasibility of implementing a deep, real-time analytics platform for metastatic breast cancer patients that can provide new insight into therapeutic opportunities. The observed clinical responses support further use and investigation of this approach.

Citation Format: Ben L. Kong, Brett E. Johnson, Jamie M. Keck, Souraya Mitri, Patrick Leyshock, Jayne M. Stommel, Kiara Siex, Marlana Klinger, Christina L. Zheng, Rochelle Williams-Belizaire, Shannon McWeeney, Jeremy Goecks, Annette Kolodzie, Alexander R. Guimaraes, George V. Thomas, Christopher L. Corless, Zahi I. Mitri, Joe W. Gray, Gordon B. Mills, Raymond C. Bergan. SMMART Program: A multi-omics tumor board with a focus on breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB010.