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Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()

Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsi...

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Autores principales: Tibau, Ariadna, López-Vilaró, Laura, Pérez-Olabarria, Maitane, Vázquez, Tania, Pons, Cristina, Gich, Ignasi, Alonso, Carmen, Ojeda, Belén, Ramón y Cajal, Teresa, Lerma, Enrique, Barnadas, Agustí, Escuin, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212250/
https://www.ncbi.nlm.nih.gov/pubmed/25379022
http://dx.doi.org/10.1016/j.neo.2014.08.012
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author Tibau, Ariadna
López-Vilaró, Laura
Pérez-Olabarria, Maitane
Vázquez, Tania
Pons, Cristina
Gich, Ignasi
Alonso, Carmen
Ojeda, Belén
Ramón y Cajal, Teresa
Lerma, Enrique
Barnadas, Agustí
Escuin, Daniel
author_facet Tibau, Ariadna
López-Vilaró, Laura
Pérez-Olabarria, Maitane
Vázquez, Tania
Pons, Cristina
Gich, Ignasi
Alonso, Carmen
Ojeda, Belén
Ramón y Cajal, Teresa
Lerma, Enrique
Barnadas, Agustí
Escuin, Daniel
author_sort Tibau, Ariadna
collection PubMed
description Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.
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spelling pubmed-42122502014-11-06 Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()() Tibau, Ariadna López-Vilaró, Laura Pérez-Olabarria, Maitane Vázquez, Tania Pons, Cristina Gich, Ignasi Alonso, Carmen Ojeda, Belén Ramón y Cajal, Teresa Lerma, Enrique Barnadas, Agustí Escuin, Daniel Neoplasia Article Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis. Neoplasia Press 2014-10-23 /pmc/articles/PMC4212250/ /pubmed/25379022 http://dx.doi.org/10.1016/j.neo.2014.08.012 Text en © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Tibau, Ariadna
López-Vilaró, Laura
Pérez-Olabarria, Maitane
Vázquez, Tania
Pons, Cristina
Gich, Ignasi
Alonso, Carmen
Ojeda, Belén
Ramón y Cajal, Teresa
Lerma, Enrique
Barnadas, Agustí
Escuin, Daniel
Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title_full Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title_fullStr Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title_full_unstemmed Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title_short Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer()()
title_sort chromosome 17 centromere duplication and responsiveness to anthracycline-based neoadjuvant chemotherapy in breast cancer()()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212250/
https://www.ncbi.nlm.nih.gov/pubmed/25379022
http://dx.doi.org/10.1016/j.neo.2014.08.012
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