title: Prognostic potential of topoisomerase IIα and HER2 in a retrospective analysis of early advanced breast cancer patients treated with adjuvant anthracycline chemotherapy.
abstract: BACKGROUND
  After surgery and anthracycline adjuvant treatment, about 60% of early advanced breast cancer patients develop recurrence. These differences in treatment outcome indicate the need to identify markers for risk of recurrence. The aim of this study was the retrospective analysis of relationship between tumour features (topoisomerase IIα (TOPOIIα), human epidermal growth factor receptor 2 (HER2), hormone receptors, cytokeratin (CK)5/6 expression and proliferation rate) and disease-free survival (DFS) of breast cancer patients treated with anthracyclines in adjuvant setting.
  
  
  METHODS
  The study was performed in the group of 172 patients (mean age: 52.8 years, T1-T2, N1-N2, M0). HER2, TOPOIIα, estrogen receptor (ER) and progesterone receptor (PgR) expression and proliferation rate were studied immunohistochemically. HER2 overexpression was confirmed by fluorescence in situ hybridisation (FISH). These data were correlated with 5-year DFS.
  
  
  RESULTS
  In univariate analysis, lower TOPOIIα expression (median value ≤ 11.9%) and tumour grade G1 + G2 were favourable prognostic factors. All tumours were classified into four subtypes: (1) lower TOPOIIα expression and G1 + G2, (2) lower TOPOIIα expression and G3, (3) higher TOPOIIα expression and G3, and (4) higher TOPOIIα expression and G1 + G2. In Cox multivariate regression analysis, tumour subtype distinguished by TOPOIIα expression and grade was independent prognostic factor for DFS. All patients (n = 52) with TOPOIIα lower expression and G1 + G2 tumours, survived 5 years without any evidence of disease.
  
  
  CONCLUSIONS
  The results suggest that lower TOPOIIα expression and lower tumour grade are favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline chemotherapy.
authors.affiliation: Department of Applied Radiobiology, Centre of Oncology, ul. Garncarska 11, 31-115 Krakow, Poland. z5biesag@cyfronet.pl
authors.forename: Beata
authors.initials: B
authors.lastname: Biesaga
authors.forename: Joanna
authors.initials: J
authors.lastname: Niemiec
authors.forename: Marek
authors.initials: M
authors.lastname: Ziobro
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczak
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007633:Keratins / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases