Topoisomerase II alpha as a marker predicting anthracyclines' activity in early breast cancer patients: ready for the primetime?
OBJECTIVE
This manuscript reviews and discusses results from randomised clinical studies evaluating topoisomerase II alpha (topo II) as a marker predicting anthracyclines' activity in early breast cancer patients.


METHODS
A Medline search has led to the identification of six phase III clinical trials, in which topo II has been retrospectively evaluated as a marker predicting anthracyclines' activity in the adjuvant setting.


RESULTS
Rates of topo II gene aberrations, in particular gene deletion, seem to vary substantially between the studies. No extensive correlation has been found between topo II gene status and protein levels. Five of the six trials suggest that topo II gene amplification is associated with increased tumour sensitivity to anthracyclines. Two of the three studies evaluating topo II gene deletions suggest that topo II deleted tumours might also derive an increased benefit from anthracyclines.


CONCLUSIONS
Current data suggest that topo II might become a predictive tool to identify patients candidate to receive anthracyclines in the adjuvant setting. Ongoing studies will likely address some pending issues which, at present, prevent the use of this marker in daily practice.
Di Leo
Angelo
A
Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy. adileo@usl4.toscana.it
Biganzoli
Laura
L
Claudino
Wederson
W
Licitra
Sara
S
Pestrin
Marta
M
Larsimont
Denis
D
D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D002869:Chromosome Aberrations; D017326:Clinical Trials, Phase III as Topic; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D018943:Anthracyclines; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II