The COXEN gene expression model with chemotherapy-specific scores (for DD-MVAC and GC) was developed to identify responders to NAC. We investigated RNA-based molecular subtypes as additional predictive biomarkers for NAC response, PFS, and OS in patients treated in S1314.
237 patients were randomized between 4 cycles of ddMVAC (51%) and GC (49%). Based on Affymetrix transcriptomic data, we determined subtypes using 3 classifiers: TCGA (k=5), Consensus (k=6), and MD Anderson (MDA; k=3) and assessed subtype association with path response to NAC and determined associations with COXEN. We also tested whether each classifier contributed additional predictive power when added to a model based on pre-defined stratification factors (PS 0 vs. 1; T2 vs. T3, T4a).
155 patients had gene expression results, received at least 3 of 4 cycles of NAC and had pT-N response based on RC. TCGA 3 group classifier BS/Neuronal, Lum, Lum infiltrated and GC COXEN score yielded the largest AUCs for pT0 (0.59 p=0.28; 0.60 p=0.18, respectively). For downstaging (<pT2), the 3 category Consensus classifier (BS/NE-like, Lum, Stroma-rich) increased the AUC from 0.57 (strat factors alone) to 0.61 (p=0.10). The MDA classifier AUC was 0.63 (p=0.18) and the GC COXEN score AUC was 0.62 (p=0.23), but neither significantly improved the AUC. There was no statistically significant association of stratification factors and subtypes with PFS or OS.
The Consensus classifier, based in part on the TCGA and MDA classifiers, modestly improved prediction for pathologic downstaging but subtypes were not associated with PFS or OS.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Nov 15 [Epub ahead of print]
Seth P Lerner, David J McConkey, Catherine M Tangen, Joshua J Meeks, Thomas W Flaig, X Hua, Siamak Daneshmand, Ajjai Shivaram Alva, M Scott Lucia, Dan Theodorescu, Amir Goldkorn, Matthew I Milowsky, W Choi, Rick Bangs, Daniel L Gustafson, Melissa Plets, Ian M Thompson
Baylor College of Medicine, Houston, TX, United States., Johns Hopkins School of Medicine, Baltimore, United States., Fred Hutchinson Cancer Center, Seattle, WA, United States., Northwestern University Feinberg School of Medic, Chicago, Illinois, United States., University of Colorado Anschutz Medical Campus, Aurora, CO, United States., National Cancer Institute, Rockville, MD, United States., USC/Norris Comprehensive Cancer Center, Los Angeles, CA, United States., University of Michigan-Ann Arbor, Ann Arbor, United States., University of Colorado School of Medicine, Denver, CO, United States., Cedars-Sinai Medical Center, Los Angeles, CA, United States., Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, Los Angeles, United States., University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States., SWOG Cancer Research Network, Portland, OR, United States., Colorado State University, Fort Collins, CO, United States., CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, United States.