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Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.
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