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Abstract
This article attempts to provide the reader with a complete overview of topoisomerase
(topo) IIα as a marker for predicting the efficacy of anthracyclines in patients with
breast cancer. In the first section of this article, in vitro data supporting the
predictive value of topo IIα are reviewed. Interestingly, these data suggest that
the interaction between HER2 and anthracycline efficacy, which has been hypothesized
in several clinical studies performed in the past decade, might depend on the concomitant
topo IIα status. Molecular pathology studies further reinforce the concept that HER2
might not be directly involved in the prediction of response to anthracyclines. They
report that topo IIα gene amplification can be found in 25%–40% of HER2/neu-amplified
tumors, while no topo II gene amplification is detected in the absence of HER2/neugene
amplification. In the second part of this article, a series of clinical studies are
reviewed and interpreted. These studies have attempted to correlate topo IIα status
with anthracycline efficacy in the adjuvant, neoadjuvant, and metastatic settings.
All of the studies evaluating the topo IIα gene suggest that gene amplification might
be associated with an increased efficacy of anthracyclines, and some of the studies
evaluating topo IIα protein find that protein overexpression might correlate with
an increased sensitivity to these compounds. Despite these findings, however, the
reported studies do not provide the proof of principle needed to authorize the use
of topo IIα as a predictive marker for standard practice. A new generation of research
is currently testing the predictive value of topo IIα. It is hoped that these projects,
which are described in the last section of the article, will clarify the role of topo
IIα in the prediction of response to anthracyclines.
Key words
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Article info
Publication history
Accepted:
June 2,
2003
Received in revised form:
May 22,
2003
Received:
April 1,
2003
Identification
Copyright
© 2003 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
