CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy.

• Type of Material: Article
• Authors: Ashley J. Schlafstein, Emory University; Allison E. Withers, Emory University; Soumon Rudra, Emory University; Diana Danelia, Emory University; Jeffrey Switchenko, Emory University; Donna Mister, Emory University; Saul Harari, Emory University; Hui Zhang, Emory University; Waaqo Daddacha, Emory University; Shahrzad Ehdaivand, Emory University; Xiaoxian Li, Emory University; Mylin Torres, Emory University; David Yu, Emory University
• Language: English
• Date: 2018
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Ashley J. Schlafstein et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1155/2018/6945129
• Title of Journal or Parent Work: International Journal of Breast Cancer
• ISSN: 2090-3170
• Volume: 2018
• Start Page: 6945129
• End Page: 6945129
• Grant/Funding Information: Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI P30CA138292 to W.J.C and NIH/NCI R01CA178999, R01CA178999S1, and WCI Brenda Nease 53237 to David S. Yu.
• Keywords: biomarkers; Breast cancer; neoadjuvant chemotherapy; CDK9
• Research Categories: Health Sciences, Oncology

Abstract

Failure to achieve pathologic complete response is associated with poor prognosis in breast cancer patients following neoadjuvant chemotherapy (NACT). However, prognostic biomarkers for clinical outcome are unclear in this patient population. Cyclin-dependent kinase 9 (CDK9) is often dysregulated in breast cancer, and its deficiency results in genomic instability. We reviewed the records of 84 breast cancer patients from Emory University's Winship Cancer Institute who had undergone surgical resection after NACT and had tissue available for tissue microarray analysis (TMA). Data recorded included disease presentation, treatment, pathologic response, overall survival (OS), locoregional recurrence free survival (LRRFS), distant-failure free survival (DFFS), recurrence-free survival (RFS), and event-free survival (EFS). Immunohistochemistry was performed on patient samples to determine CDK9 expression levels after NACT. Protein expression was linked with clinical data to determine significance. In a Cox proportional hazards model, using a time-dependent covariate to evaluate the risk of death between groups beyond 3 years, high CDK9 expression was significantly associated with an increase in OS (HR: 0.26, 95% CI: 0.07-0.98, p=0.046). However, Kaplan-Meier curves for OS, LRRFS, DFFS, RFS, and EFS did not reach statistical significance. The results of this study indicate that CDK9 may have a potential role as a prognostic biomarker in patients with breast cancer following NACT. However, further validation studies with increased sample sizes are needed to help elucidate the prognostic role for CDK9 in the management of these patients.