CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy
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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.1155/2018/6945129 |
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| author | Ashley J. Schlafstein Allison E. Withers Soumon Rudra Diana Danelia Jeffrey M. Switchenko Donna Mister Saul Harari Hui Zhang Waaqo Daddacha Shahrzad Ehdaivand Xiaoxian Li Mylin A. Torres David S. Yu |
| author_facet | Ashley J. Schlafstein Allison E. Withers Soumon Rudra Diana Danelia Jeffrey M. Switchenko Donna Mister Saul Harari Hui Zhang Waaqo Daddacha Shahrzad Ehdaivand Xiaoxian Li Mylin A. Torres David S. Yu |
| author_sort | Ashley J. Schlafstein |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-33a4a2a95b42440e8020da2048abadae |
| institution | Kabale University |
| issn | 2090-3170 2090-3189 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-33a4a2a95b42440e8020da2048abadae2025-02-03T05:50:48ZengWileyInternational Journal of Breast Cancer2090-31702090-31892018-01-01201810.1155/2018/69451296945129CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant ChemotherapyAshley J. Schlafstein0Allison E. Withers1Soumon Rudra2Diana Danelia3Jeffrey M. Switchenko4Donna Mister5Saul Harari6Hui Zhang7Waaqo Daddacha8Shahrzad Ehdaivand9Xiaoxian Li10Mylin A. Torres11David S. Yu12Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Biostatistics and Bioinformatics, Rollins School of Public Health and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Pathology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Pathology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Pathology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USAFailure 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.http://dx.doi.org/10.1155/2018/6945129 |
| spellingShingle | Ashley J. Schlafstein Allison E. Withers Soumon Rudra Diana Danelia Jeffrey M. Switchenko Donna Mister Saul Harari Hui Zhang Waaqo Daddacha Shahrzad Ehdaivand Xiaoxian Li Mylin A. Torres David S. Yu CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy International Journal of Breast Cancer |
| title | CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy |
| title_full | CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy |
| title_fullStr | CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy |
| title_full_unstemmed | CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy |
| title_short | CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy |
| title_sort | cdk9 expression shows role as a potential prognostic biomarker in breast cancer patients who fail to achieve pathologic complete response after neoadjuvant chemotherapy |
| url | http://dx.doi.org/10.1155/2018/6945129 |
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