Abstract LB010: SMMART Program: A multi-omics tumor board with a focus on breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.LB010-LB010
• Main Authors: Kong, Ben L., Johnson, Brett E., Keck, Jamie M., Mitri, Souraya, Leyshock, Patrick, Stommel, Jayne M., Siex, Kiara, Klinger, Marlana, Zheng, Christina L., Williams-Belizaire, Rochelle, McWeeney, Shannon, Goecks, Jeremy, Kolodzie, Annette, Guimaraes, Alexander R., Thomas, George V., Corless, Christopher L., Mitri, Zahi I., Gray, Joe W., Mills, Gordon B., Bergan, Raymond C.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-LB010

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 pro