Changes of topoisomerase IIalpha expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival

Clin Cancer Res. 2006 Mar 1;12(5):1501-6. doi: 10.1158/1078-0432.CCR-05-0978.


Purpose: To assess the value of changes in the expression of topoisomerase IIalpha (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy.

Patients and methods: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses.

Results: Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P < 0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P < 0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors.

Conclusion: Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cyclophosphamide / therapeutic use
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Epirubicin / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Mastectomy
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / metabolism
  • Prognosis
  • Proto-Oncogene Mas
  • Receptor, ErbB-2 / metabolism
  • Stereoisomerism


  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Epirubicin
  • Cyclophosphamide
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • Fluorouracil

Supplementary concepts

  • FEC protocol