Abstract PD9-04: Identification of biomarkers associated with therapeutic resistance: Quantitative protein/phosphoprotein analysis of ~750 patients across 8 arms of the neoadjuvant I-SPY 2 TRIAL for high-risk early stage breast cancer

摘要: Background: The goal of I-SPY 2 is to rapidly test novel therapies in addition standard care high-risk breast cancer patients. It has resulted increasing response rates, where pCR rates TNBC and HR-HER2+ subsets have reached ~60% ~75%, respectively. Yet, there remains a sizeable subset non-responders, especially among HR+ Identification ‘universal’ resistance mechanisms may guide rational selection agents improve these patient9s outcomes. Thus, we analyzed reverse phase protein array (RPPA) based quantitative protein/phosphoprotein data across arms assess whether are common rendering cancers resistant all agent classes tested date. Methods: 736 patients (260 HR+HER2-, 252 TN, 142 82 HR-HER2+; over 8 arms: 194 Ctr, 105 neratinib (N), 63 veliparib/carboplatin (VC), 128 AMG386 (anti-ANG1/2), 87 MK2206 (anti-AKT), 43 TH/pertuzumab (P), 49 TDM1/P, 67 pembrolizumab (Pembro)) with RPPA at the pre-treatment time point were considered for this analysis. 141 endpoints representing key pathways assessed association using logistic regression modeling, HR, HER2 treatment arm as covariates (likelihood ratio test; p Citation Format: Julia Wulfkuhle, Denise Wolf, Christina Yau, Lamorna Brown-Swigart, Rosa I Gallagher, Gillian Hirst, Laura Sit, Smita Asare, TRIAL Investigators, Nola Hylton, Angela DeMichele, Douglas Yee, Jo Chien, Hope Rugo, John Park, Kathy Albain, Rita Nanda, Debu Tripathy, Richard Schwab, Don Berry, Esserman, van t9 Veer, Emanual Petricoin, III. biomarkers associated therapeutic resistance: Quantitative analysis ~750 neoadjuvant early stage [abstract]. In: Proceedings 2020 San Antonio Breast Cancer Virtual Symposium; Dec 8-11; Antonio, TX. Philadelphia (PA): AACR; Res 2021;81(4 Suppl):Abstract nr PD9-04.