TY - JOUR
T1 - CDK9 expression shows role as a potential prognostic biomarker in breast cancer patients who fail to achieve pathologic complete response after neoadjuvant chemotherapy
AU - Schlafstein, Ashley J.
AU - Withers, Allison E.
AU - Rudra, Soumon
AU - Danelia, Diana
AU - Switchenko, Jeffrey M.
AU - Mister, Donna
AU - Harari, Saul
AU - Zhang, Hui
AU - Daddacha, Waaqo
AU - Ehdaivand, Shahrzad
AU - Li, Xiaoxian
AU - Torres, Mylin A.
AU - Yu, David S.
N1 - Funding Information:
Multiple contributors aided in designing and completing various aspects of the study. Dr. Shahrzad Ehdaivand read sample sections from FFPE tissue blocks to identify regions of invasive tumor for TMA construction. Development of the TMA was accomplished with the help of the Ms. Dianne Alexis at the Winship Pathology Core Lab. Ms. Alexis also assisted with IHC protocol development and TMA slide staining. TMA slides for CDK9 were interpreted by Emory pathology fellow, Dr. Saul Harari. Statistical analysis was performed by Dr. Jeff Switchenko. Figures were created using statistical software R. Research reported in this publication was supported in part by the Biostatistics and Bioinforma-tics 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.
Funding Information:
Multiple contributors aided in designing and completing various aspects of the study. Dr. Shahrzad Ehdaivand read sample sections from FFPE tissue blocks to identify regions of invasive tumor for TMA construction. Development of the TMA was accomplished with the help of the Ms. Dianne Alexis at the Winship Pathology Core Lab. Ms. Alexis also assisted with IHC protocol development and TMA slide staining. TMA slides for CDK9 were interpreted by Emory pathology fellow, Dr. Saul Harari. Statistical analysis was performed by Dr. Jeff Switchenko. Figures were created using statistical software R. 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.
Publisher Copyright:
Copyright © 2018 Ashley J. Schlafstein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1155/2018/6945129
DO - 10.1155/2018/6945129
M3 - Article
AN - SCOPUS:85059813808
SN - 2090-3170
VL - 2018
JO - International Journal of Breast Cancer
JF - International Journal of Breast Cancer
M1 - 6945129
ER -
