Real-world Evidence of Diagnostic Testing and Treatment Patterns in US Patients With Breast Cancer With Implications for Treatment Biomarkers From RNA Sequencing Data

Abstract

INTRODUCTION We performed a retrospective analysis of longitudinal real-world data (RWD) from breast cancer patients to replicate results from clinical studies and demonstrate the feasibility of generating real-world evidence. We also assessed the value of transcriptome profiling as a complementary tool for determining molecular subtypes. PATIENTS AND METHODSDe-identified, longitudinal data were analyzed after abstraction from U.S. breast cancer patient records structured and stored in the Tempus database. Demographics, clinical characteristics, molecular subtype, treatment history, and survival outcomes were assessed according to strict qualitative criteria. RNA sequencing and clinical data were used to predict molecular subtypes and signaling pathway enrichment. RESULTSThe clinical abstraction cohort (n=4,000) mirrored U.S. breast cancer demographics and clinical characteristics indicating feasibility for RWE generation. Among HER2+ patients, 74.2% received anti-HER2 therapy, with ~70% starting within 3 months of a positive test result. Most non-treated patients were early stage. In this RWD set, 31.7% of patients with HER2+ IHC had discordant FISH results recorded. Among patients with multiple HER2 IHC results at diagnosis, 18.6% exhibited intra-test discordance. Through development of a wholetranscriptome model to predict IHC receptor status in the molecular sequenced cohort (n=400), molecular subtypes were resolved for all patients (n=36) with equivocal HER2 statuses from abstracted test results. Receptor-related signaling pathways were differentially enriched between clinical molecular subtypes.CONCLUSION RWD in the Tempus database mirrors the overall U.S. breast cancer population. These results suggest real-time, RWD analyses are feasible in a large, highly heterogeneous database. Furthermore, molecular data may aid deficiencies and discrepancies observed from breast cancer RWD.

Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers

“…Clinical data were extracted from the Tempus Labs (Chicago, IL) real-world oncology database, as previously described 12 (Data Supplement).…”

“…Tumor samples were clinically profiled at a College of American Pathologists-accredited, Clinical Laboratory Improvement Amendments-certified laboratory (Tempus Labs, Chicago, IL) using a single platform. Tissue-based NGS with the Tempus xT laboratory developed test was performed on DNA and RNA isolated from formalin-fixed, paraffin-embedded tumor samples using the NovaSeq and HiSeq platforms (Illumina, San Diego, CA), similar to previously described methods 12 , 13 (Data Supplement).…”

The Friends of Cancer Research Real‐World Data Collaboration Pilot 2.0: Methodological Recommendations from Oncology Case Studies

“…The contributing partners included: ASCO CancerLinQ/ConcertAI, [10][11][12][13] Cancer Research Network, 14 COTA, 15 IQVIA, 16 Ontada (formerly McKesson), 17 SEER-Medicare, 18 Syapse, 19 and Tempus. 20 In addition, Flatiron Health, Mayo Clinic, OptumLabs, and Aetion also contributed to the early phase study design. Data curation included approaches that were unique to each participant based on availability, including natural language processing, artificial intelligence tools, technology enabled abstraction, and chart review.…”

Validation of Genomic and Transcriptomic Models of Homologous Recombination Deficiency in a Real-World Pan-Cancer Cohort

“…All underwent DNA sequencing based on the Tempus|xT targeted panel (n = 48,827), Tempus|xO (n = 9), or Tempus|xE whole-exome panel (n = 17) these samples, 47,997 had RNA sequencing available. Sample preparation, DNA sequencing, and RNA sequencing for each assay were conducted as previously described (28)(29)(30)(31)(32).…”