Abstract P5-12-12: ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients

Abstract

Abstract Prognostic biomarkers are capable to predict survival and predictive biomarkers are capable to predict therapy response. Systemic therapy of breast cancer can include chemotherapy, hormonal therapy, and targeted therapy. Here, we report the initial release of the first online available tool capable to identify gene expression based predictive biomarkers using transcriptomic data of a large set of breast cancer patients. Published gene expression data of 44 publicly available datasets was integrated with treatment data into a unified database. The classification is based on either author-reported pathological complete response (n=1,775) or relapse-free survival status at five years (n=1,329). Treatment data includes chemotherapy (n=2,108), endocrine therapy (n=971), and anti-HER2 therapy (n=267). The transcriptomic database includes 20,089 unique genes and 54,675 probe sets. Gene expression and therapy response are compared using receiver operating characteristics and Mann-Whitney tests. We demonstrate the utility of the tool by validating a set of established biomarkers including TP53 for chemotherapy in luminal breast cancer (p=5.2e-20, AUC=0.77), ERBB2 for trastuzumab therapy (p=8.4e-04, AUC=0.629), and PGR for hormonal therapy (p=8.6e-05, AUC=0.7). The tool is designed to validate and rank new predictive biomarker candidates in real time. By analyzing the selected genes in a large set of independent patients, one can select the most robust candidate and quickly eliminate those which are most likely to fail in a clinical setting. The analysis tool is accessible at www.rocplot.org/breast. Citation Format: Győrffy B, Fekete J. ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-12.