@article{3087993,
    title = "Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: Pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials",
    author = "Fountzilas, G. and Dafni, U. and Bobos, M. and Kotoula, V. and Batistatou, A. and Xanthakis, I. and Papadimitriou, C. and Kostopoulos, I. and Koletsa, T. and Tsolaki, E. and Televantou, D. and Timotheadou, E. and Koutras, A. and Klouvas, G. and Samantas, E. and Pisanidis, N. and Karanikiotis, C. and Sfakianaki, I. and Pavlidis, N. and Gogas, H. and Linardou, H. and Kalogeras, K.T. and Pectasides, D. and Dimopoulos, M.A.",
    journal = "BMC Cancer",
    year = "2013",
    volume = "13",
    issn = "1471-2407",
    doi = "10.1186/1471-2407-13-163",
    keywords = "anthracycline;  cyclophosphamide;  DNA topoisomerase (ATP hydrolysing);  epidermal growth factor receptor 2;  epirubicin;  estrogen receptor;  fluorouracil;  Ki 67 antigen;  methotrexate;  paclitaxel;  progesterone receptor;  topoisomerase II alpha;  unclassified drug, adult;  aged;  article;  breast cancer;  cancer adjuvant therapy;  cancer grading;  cancer hormone therapy;  cancer prognosis;  cancer size;  cancer survival;  centromere;  centromere 17;  controlled study;  disease free survival;  female;  fluorescence in situ hybridization;  gene amplification;  gene deletion;  gene dosage;  gene location;  genetic gain;  histopathology;  human;  human tissue;  immunohistochemistry;  major clinical study;  menopause;  multiple cycle treatment;  oncogene neu;  overall survival;  phase 3 clinical trial (topic);  phenotype;  protein expression;  randomized controlled trial (topic);  survival rate;  topoisomerase II alpha gene, Adult;  Aged;  Anthracyclines;  Antigens, Neoplasm;  Antineoplastic Combined Chemotherapy Protocols;  Breast Neoplasms;  Centromere;  Chromosome Aberrations;  Chromosomes, Human, Pair 17;  Clinical Trials, Phase III as Topic;  DNA Topoisomerases, Type II;  DNA-Binding Proteins;  Female;  Gene Dosage;  Humans;  Immunohistochemistry;  In Situ Hybridization, Fluorescence;  Middle Aged;  Neoplasm Grading;  Neoplasm Staging;  Odds Ratio;  Prognosis;  Randomized Controlled Trials as Topic;  Receptor, erbB-2;  Tumor Markers, Biological;  Young Adult",
    abstract = "Background: The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy.Methods: Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ≥2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated.Results: HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death.Conclusion: HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202. © 2013 Fountzilas et al.; licensee BioMed Central Ltd."
}