TOP2A protein by quantitative immunofluorescence as a predictor of response to epirubicin in the neoadjuvant treatment of breast cancer

Future Oncol. 2013 Oct;9(10):1477-87. doi: 10.2217/fon.13.103.

Abstract

Aim: Anthracyclines are commonly used in breast cancer, although they lack validated predictive biomarkers. We explored the interaction between TOP2A protein by quantitative immunofluorescence (QIF) and anthracycline sensitivity.

Patients & methods: Patients with estrogen receptor-negative breast cancer received neoadjuvant epirubicin. Pretreatment biopsies were analyzed using AQUA(®). Total, cytoplasmic (C) and nuclear (N) TOP2A protein concentrations were expressed as QIF scores and compared with pathologic complete response (pCR), TOP2A by immunohistochemistry, TOP2A mRNA, TOP2A and HER2 gene status, and Ki-67 level.

Results: In total, 76 cases were assessable. C, N, and total scores did not correlate with pCR, or other markers. The N:C ratio differed significantly by HER2 status. No pCRs occurred in patients in the lowest N:C quartile.

Conclusion: Although no relevant correlation between TOP2A QIF scores and pCR was found, N:C ratio may have a negative predictive role, and may merit further exploration in a multifactorial predictive model that includes tumor and host factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epirubicin / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry
  • Neoadjuvant Therapy
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Protein Transport
  • Topoisomerase II Inhibitors / therapeutic use*

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Topoisomerase II Inhibitors
  • Epirubicin
  • DNA Topoisomerases, Type II
  • TOP2A protein, human