Abstract GS3-05: Classification of triple negative breast cancer (TNBC) by DNA damage immune response (DDIR) signature and homologous recombination deficiency (HRD) status: Analysis of SWOG S9313 adjuvant trial

Autor: Yesim Gökmen-Polar, Lajos Pusztai, Richard D. Kennedy, Alastair M. Thompson, Priyanka Sharma, Kirsten Timms, Daniel F. Hayes, Gabriel N. Hortobagyi, Peggy L. Porter, Debu Tripathy, Hannah M. Linden, Shane R. Stecklein, Andrew K. Godwin, William E. Barlow, Sunil Badve
Rok vydání: 2021
Předmět:
Zdroj: Cancer Research. 81:GS3-05
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs20-gs3-05
Popis: Introduction/Aims: DDIR signature, HRD, and stromal tumor infiltrating lymphocytes (sTIL) have each been associated with favorable outcomes in early stage TNBC. We assessed the overlap between these markers and created prognostic categories based on their combined use in a prospective trial of TNBC patients uniformly treated with adjuvant doxorubicin (A) and cyclophosphamide (C) on the SWOG S9313 trial. Methods: SWOG S9313 trial accrued 3,125 women with early stage breast cancer to two alternative dose schedules of AC, with no difference in outcomes between the two arms. 425 centrally determined TNBC cases from S9313 were identified. DDIR signature (score ≥ 0.3681 = DDIR+, Almac Diagnostic Services), HRD status (score ≥ 42 = HRD+, Myriad Genetics), and sTIL were assessed. Gene expression data (Xcel™ array) was subjected to claraT V3.0.0 biological signature analysis (Almac Diagnostic Services), and co-expression cluster analysis was used to identify signatures associated with DDIR and HRD status. The impact of dual classification by DDIR and HRD status (Group 1: DDIR+/HRD+, Group 2: DDIR+/HRD-, Group 3: DDIR-/HRD+, Group 4: DDIR-/HRD-) on disease free survival (DFS) and overall survival (OS) was examined using Cox regression with adjustment for randomized treatment assignment and nodal status. Results: For the 425 patients, median age was 45 years, 33% were node-positive, and 5-year DFS and OS were 74% and 82%, respectively. DDIR and HRD status was available for 89% each, sTIL% was available for 99%, and all three markers were available for 77% (328/425) of patients. 60% were DDIR+ and 65% HRD+. Among DDIR- tumors, 58% were HRD+. sTIL% was associated with DDIR status (P Table 1Immune-Enriched GroupsImmune-Deplete GroupsGroup 1 DDIR+/HRD+ N=137 (42%)Group 2 DDIR+/HRD- N=59 (18%)Group 3 DDIR-/HRD+ N=77 (23%)Group 4 DDIR-/HRD- N=55 (17%)5-year DFS82%74%74%56%P=0.001 (Group 1 vs 4); P=0.006 (Group 2 vs 4); P=0.016 (Group 3 vs 4); P=NS (Groups 1 vs 2, 1 vs 3, and 2 vs 3)5-year OS88%86%83%69%P=0.001 (Group 1 vs 4); P=0.003 (Group 2 vs 4); P=0.026 (Group 3 vs 4); P=NS (Group 1 vs 2, 1 vs 3, and 2 vs 3)Median sTIL (%)20%20%5%5%P Citation Format: Shane R Stecklein, William Barlow, Lajos Pusztai, Kirsten Timms, Richard Kennedy, Sunil Badve, Yesim Gökmen-Polar, Peggy Porter, Hannah Linden, Debu Tripathy, Gabriel N Hortobagyi, Andrew K Godwin, Alastair Thompson, Daniel Hayes, Priyanka Sharma. Classification of triple negative breast cancer (TNBC) by DNA damage immune response (DDIR) signature and homologous recombination deficiency (HRD) status: Analysis of SWOG S9313 adjuvant trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-05.
Databáze: OpenAIRE
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