GSE137356 Validation of the DNA Damage Immune Response (DDIR) Signature in Triple-Negative Breast Cancer (TNBC) Patients from the SWOG 9313c Trial

Contributors : P Sharma ; W E Barlow ; A K Godwin ; E E Parkes ; L A Knight ; S M Walker ; R D Kennedy ; D P Harkin ; G E Logan ; C J Steele ; S M Lambe ; S Badve ; Y Gokmen-Polar ; H B Pathak ; K Isakova ; H M Linden ; P Porter ; L Pusztai ; A M Thompson ; D Tripathy ; G N Hortobagyi ; D F HayesSeries Type : Expression profiling by arrayOrganism : Homo sapiensPurpose: The purpose of this study was to independently validate two biomarkers, a 44-gene DNA Damage Immune Response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in TNBC patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313. Materials& Methods: 425 centrally determined TNBC cases from S9313 were identified. DDIR signature was performed on RNA isolated from FFPE tumor tissue (n=381), and samples were classified as DDIR-negative or positive using predefined cutoffs. Evaluation of sTILs was performed as previously described. Markers were tested for prognostic value for disease-free and overall survival (DFS, OS) using Cox regression models adjusted for treatment assignment nodal status and tumor size. Results: Among 425 TNBC patients, median age was 45 years, and 33% were node-positive. DDIR was successfully tested in 90% (381/425) of cases, of which 62% were DDIR signature-positive. DDIR signature positivity was associated with improved DFS (HR=0.67; 95% CI 0.48 –0.92, P=0.014) and OS (HR=0.61; 95% CI 0.43–0.89, P=0.009). sTILs dens...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research