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

Autor: Fernandes LE; Tempus Labs, Chicago, IL., Epstein CG; Tempus Labs, Chicago, IL., Bobe AM; Tempus Labs, Chicago, IL., Bell JSK; Tempus Labs, Chicago, IL., Stumpe MC; Tempus Labs, Chicago, IL., Salazar ME; Tempus Labs, Chicago, IL., Salahudeen AA; Tempus Labs, Chicago, IL., Pe Benito RA; Tempus Labs, Chicago, IL., McCarter C; Tempus Labs, Chicago, IL., Leibowitz BD; Tempus Labs, Chicago, IL., Kase M; Tempus Labs, Chicago, IL., Igartua C; Tempus Labs, Chicago, IL., Huether R; Tempus Labs, Chicago, IL., Hafez A; Tempus Labs, Chicago, IL., Beaubier N; Tempus Labs, Chicago, IL., Axelson MD; Tempus Labs, Chicago, IL., Pegram MD; Stanford Comprehensive Cancer Institute, Stanford University School of Medicine, Stanford, CA., Sammons SL; Department of Medicine, Duke University Medical Center, Duke University, Durham, NC., O'Shaughnessy JA; Baylor University Medical Center, Texas Oncology and US Oncology, Dallas, TX., Palmer GA; Tempus Labs, Chicago, IL. Electronic address: publications@Tempus.com.
Jazyk: angličtina
Zdroj: Clinical breast cancer [Clin Breast Cancer] 2021 Aug; Vol. 21 (4), pp. e340-e361. Date of Electronic Publication: 2020 Dec 18.
DOI: 10.1016/j.clbc.2020.11.012
Abstrakt: Objective/background: We performed a retrospective analysis of longitudinal real-world data (RWD) from patients with breast cancer 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.
Methods: De-identified, longitudinal data were analyzed after abstraction from records of patients with breast cancer in the United States (US) 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.
Results: The clinical abstraction cohort (n = 4000) mirrored the demographics and clinical characteristics of patients with breast cancer in the US, indicating feasibility for RWE generation. Among patients who were human epidermal growth factor receptor 2-positive (HER2 + ), 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 + immunohistochemistry (IHC) had discordant fluorescence in situ hybridization results recorded. Among patients with multiple HER2 IHC results at diagnosis, 18.6% exhibited intra-test discordance. Through development of a whole-transcriptome 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.
Conclusions: RWD in the Tempus database mirrors the overall population of patients with breast cancer in the US. These results suggest that 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.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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