Mode of Action

Oestrogens are the end-products of a complex synthetic sequence of steroid intermediates, involving the key enzyme, aromatase. The aromatase enzyme is responsible for the final step in oestrogen synthesis, namely, the conversion of the androgens, androstenedione and testosterone, into the oestrogens, oestrone and oestradiol, respectively, an action which is selectively inhibited by ARIMIDEX (Figure 1). Aromatase belongs to the group of cytochrome P-450 enzymes, which are involved in the biosynthesis of aldosterone, cortisol and androgens. It is found in peripheral tissues, such as muscle, fat and liver, and within the breast tumour itself.

  

Figure 1: Biosynthesis of oestrogens

The inhibition of oestrogen production provides effective therapy for women with hormone-dependent breast cancer. Although the source of oestrogens in premenopausal women is predominantly ovarian, after the menopause, oestradiol is synthesised peripherally through aromatisation of adrenal androgens to oestrogens (Figure 1).

References

1. Masamura S, Adlercreutz H, Harvey H, et al. Aromatase inhibitor development for treatment of breast cancer. Breast Cancer Res Treat 1994;33:19–26.

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Review period : 12 months
Last reviewed : June 2009