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Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation?

Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation?

Lonning PE

Eur J Cancer, 2009, 45, 527-535

This interesting review article discusses the well-known clinical finding that some patients with breast cancers resistant to one aromatase inhibitor (AI) may respond to a second AI, usually of the steroidal type (e.g. exemestane). Why this should be so is more difficult to explain since the main mechanism of action of all AIs is to suppress plasma oestradiol. The reviewer took us through the features of the three best known AIs (letrozole, anastrozole and exemestane) and examined the evidence from several small Phase II trials, which do conclusively show an approximate 25-30% clinical benefit rate from the steroidal AIs following resistance to non-standard AIs. Several possible mechanisms are reviewed that could explain the partial lack of cross-resistance including type of previous therapy, biological characteristics of tumour, pharmacological efficacy of the different AIs, bioavailability of AIs in tumour tissue, aromatase enzyme variants and different promoters, and the importance of the irreversibility of AIs such as exemestane or its partial androgen agonistic effects. However, none of these is convincing. A final possible explanation is that different AIs may have distinct effects on growth factor regulation using techniques such as mRNA expression profiling using micro-arrays in cell culture systems. Some evidence is provided here but much more work needs to be done before we can explain this clinical observation.

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Article Details
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Author:Barrett-Lee, Peter
Publication:Advances in Breast Cancer
Article Type:Brief article
Geographic Code:1USA
Date:Mar 1, 2009
Words:241
Previous Article:31st Annual San Antonio Breast Cancer Symposium.
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