Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer

Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer

Amplification or deletion of the topoisomerase IIα (TOP2A) gene in breast cancer has been related with responsiveness to anthracyclines-based chemotherapy. The purpose of this study was to evaluate the predictive value of TOP2A gene for the efficacy of neo-adjuvant anthracycline in a population with...

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Bibliographic Details
Published in:Pathology, research and practice Vol. 210; no. 10; pp. 675 - 679
Main Authors: Almeida, Daniela, Gerhard, Renê, Leitão, Dina, Davilla, Cristina, Damasceno, Margarida, Schmitt, Fernando
Format: Journal Article
Language:English
Published: Germany Elsevier GmbH 01-10-2014
Subjects:
Adult
Aged
Anthracycline
Anthracyclines - pharmacology
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Disease-Free Survival
DNA Topoisomerases, Type II - genetics
DNA Topoisomerases, Type II - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Female
Gene Amplification - genetics
Gene Expression Regulation, Neoplastic - drug effects
Genetic Testing
Humans
Male
Middle Aged
Poly-ADP-Ribose Binding Proteins
Predictive marker
Receptor, ErbB-2 - metabolism
Topoisomerase II alfa
Treatment Outcome
Young Adult
Breast cancer
Topoisomerase II alfa
Anthracycline
Predictive marker
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Summary:Amplification or deletion of the topoisomerase IIα (TOP2A) gene in breast cancer has been related with responsiveness to anthracyclines-based chemotherapy. The purpose of this study was to evaluate the predictive value of TOP2A gene for the efficacy of neo-adjuvant anthracycline in a population with locally advanced breast cancer. Sixty-two patients were included, and the status of TOP2A gene was determined by in situ hybridization method. Treatment efficacy was determined by clinical and pathological response and overall survival. TOP2A gene alterations were found in 22.6% (21.0% of cases with amplification and 1.6% with deletion), and these tumors were biologically more aggressive, with higher nuclear grade, more frequently with HER2 amplification and inflammatory type. Also in these tumors response to chemotherapy appeared to be increased. There was a higher clinical and pathological response rate (complete pathological response of 21.4% vs. 8.3%), a trend toward longer progression-free survival (82.51 vs. 63.12 months) and a trend to increased overall survival (92.08 months; 95% CI 82.81–101.35 vs. 73.40 months; 95% CI 63.44–83.36; p=0.113). These results corroborate that the TOP2A gene alterations may play an important role in determining anthracycline sensitivity in breast cancer.
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ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2014.06.017