title: The predictive and prognostic significance of pre- and post-treatment topoisomerase IIα in anthracycline-based neoadjuvant chemotherapy for local advanced breast cancer.
abstract: OBJECTIVE
  To investigate the predictive and prognostic value of topoisomerase IIα (Topo IIα, Topo II) expression in the primary tumors and residual tumors of local advanced breast cancer (LABC) patients being treated with anthracycline-based neoadjuvant chemotherapy (NCT).
  
  
  METHODS
  The data from 283 LABC patients who had been treated with anthracycline-based neoadjuvant chemotherapy were collected. The expression of Topo IIα, HER-2 and other biomarkers was determined via immunohistochemical analysis in pre- and post-chemotherapy specimens. The status of pre-treatment biomarkers was correlated with the clinical response determined by the RECIST 1.1 criteria, whereas the post-treatment biomarkers were studied for prognostic value using the Cox model.
  
  
  RESULTS
  By analyzing the complete data from 99 patients, the co-expression of HER-2/Topo IIα was found to be significantly correlated with the clinical response to chemotherapy (Logistic regression P = 0.042). Notably, a 20% alteration in the Topo IIα status during neoadjuvant chemotherapy was found, which could also influence the sensitivity to treatment. With a survival analysis performed in 245 patients with residual tumors after NCT, node metastasis, HER-2 and Ki-67 were independent predictors of patient outcome. However, post-treatment Topo IIα expression demonstrated significant prognostic value in HER-2+ patients (P = 0.002). A relatively lower disease-free survival and overall survival was observed in HER-2+/Topo- patients (log rank P = 0.010 for DFS and P < 0.001 for OS).
  
  
  CONCLUSIONS
  Topo IIα, together with HER-2, might help to select for patients who could benefit from anthracycline-based neoadjuvant chemotherapy and identify non-complete responders at a higher risk of disease recurrence or death.
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: C M
authors.initials: CM
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: Z M
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018943:Anthracyclines / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D004250:DNA Topoisomerases, Type II / Q000032:analysis* / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000302:isolation & purification; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008197:Lymph Node Excision; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000302:isolation & purification; D012189:Retrospective Studies
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human