title: Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer.
abstract: 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.
authors.affiliation: Medical Oncology Department, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Almeida
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto and Department of Pathology, University Health Network, Toronto, Canada.
authors.forename: Renê
authors.initials: R
authors.lastname: Gerhard
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Leitão
authors.affiliation: Medical Oncology Department, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Davilla
authors.affiliation: Medical Oncology Department, Centro Hospitalar de São João, Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Damasceno
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto and Department of Pathology, University Health Network, Toronto, Canada. Electronic address: Fernando.Schmitt@uhn.ca.
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human
keywords: Anthracycline; Breast cancer; Predictive marker; Topoisomerase II alfa