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Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer
Tibau, Ariadna (Institut d'Investigació Biomèdica Sant Pau)
López Vilaró, Laura (Institut d'Investigació Biomèdica Sant Pau)
Pérez-Olabarria, Maitane (Institut d'Investigació Biomèdica Sant Pau)
Vázquez, Tania (Institut d'Investigació Biomèdica Sant Pau)
Pons, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Gich Saladich, Ignasi (Institut d'Investigació Biomèdica Sant Pau)
Alonso, Carmen (Institut d'Investigació Biomèdica Sant Pau)
Ojeda, Belén (Institut d'Investigació Biomèdica Sant Pau)
Ramón y Cajal, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Lerma Puertas, Enrique (Institut d'Investigació Biomèdica Sant Pau)
Barnadas i Molins, Agustí (Institut d'Investigació Biomèdica Sant Pau)
Escuin, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date: 2014
Abstract: 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.
Note: Número d'acord de subvenció RTICC RD12-0036-0076
Note: Número d'acord de subvenció ISCIII/PI10-0307
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: CEP17, chromosome 17 centromere enumeration probe ; CI, confidence interval ; CISH, chromogenic in situ hybridization ; DFS, disease-free survival ; EC-D, epirubicin (90 mg/m 2) and cyclophosphamide (600 mg/m 2) followed by docetaxel (100 mg/m 2) ; ER, estrogen receptor ; FEC75, fluorouracil (600 mg/m 2), epirubicin (75 mg/m 2), and cyclophosphamide (600 mg/m 2) ; FISH, fluorescence in situ hybridization ; HR, hazard ratio ; HER2, human epidermal growth factor receptor 2 ; OR, odds ratio ; OS, overall survival ; Pcr, pathologic complete response ; PR, progesterone receptor ; TOP2A, topoisomerase II alpha
Published in: Neoplasia (New York, N.Y.), Vol. 16 (october 2014) , p. 861-867, ISSN 1476-5586

DOI: 10.1016/j.neo.2014.08.012
PMID: 25379022

7 p, 303.7 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-03-06, last modified 2020-11-03

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