Topoisomerase 2 alpha and the case for individualized breast cancer therapy

Ann Surg Oncol. 2010 May;17(5):1392-7. doi: 10.1245/s10434-009-0855-0. Epub 2010 Mar 9.

Abstract

Background: Many patients with breast cancer receive no benefit from their treatment. This has led to a search for novel therapeutic targets whose identification may facilitate a more tailored approach, thereby avoiding unnecessary toxicity. Of these, topoisomerase 2 alpha (TOP2A), located at the HER2/neu amplicon on chromosome 17, has generated particular interest because its expression has been shown to correlate with response to anthracycline-based therapies.

Methods: We evaluated the relationship between TOP2A and its collocated gene, HER2/neu, and summarized the evidence for and against confining anthracycline-based therapies to those patients who demonstrate increased expression or amplification of these targets.

Results: The emerging consensus supports the restriction of anthracyclines to those patients who are HER2/neu positive, with the evidence suggesting that alterations in the status of TOP2A are almost completely restricted to this group of patients.

Conclusions: It seems increasingly likely that response to anthracyclines is predicated on these alterations.

MeSH terms

  • Anthracyclines / therapeutic use*
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Amplification
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Precision Medicine
  • Prognosis
  • Receptor, ErbB-2 / metabolism*

Substances

  • Anthracyclines
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human