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Aromatase inhibitors and models for breast cancer

  • Angela Brodie
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Two approaches that are used to ameliorate the growth effects of oestrogens on primary and metastastic breast cancers are the inhibition of oestrogen action by compounds interacting with oestrogen receptors (ERs; antioestrogens) and the inhibition of oestrogen synthesis by inhibitors of the enzyme, aromatase. Treatment with the antioestrogen, tamoxifen, has been an important therapeutic advance in breast cancer management for patients with ER-positive tumours. However, concerns exist about the long-term use of this antioestrogen. Although tamoxifen functions as an ER antagonist, it also exhibits weak or partial agonist properties. The antioestrogenic activity of tamoxifen is limited to its effects on breast tumour cells whereas in other regions of the body tamoxifen may actually function as an oestrogen agonist. This can lead to increased risk of hyperplasia of the endometrium and occasionally cancer and increased risk of strokes [1], [2]. These agonist effects of tamoxifen were realized from its inception [3]. Because of these concerns, we proposed selective inhibition of aromatase to reduce oestrogen production as a different strategy that is unlikely to be associated with oestrogenic effects. For this reason, aromatase inhibition could have greater antitumour efficacy than tamoxifen. The selective approach would not interfere with other cytochrome P450 enzymes involved in the synthesis of essential hormones such as cortisol and aldosterone.

Keywords

Breast Cancer Aromatase Inhibitor Aromatase Activity Letrozole Treatment Aromatase Inhibitor Letrozole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Angela Brodie
    • 1
  1. 1.Department of Pharmacology & Experimental TherapeuticsUniversity of Maryland, School of MedicineBaltimoreUSA

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