Worldwide, breast cancer is the commonest cause of cancer and cancer mortality in women Ferlay 2000. Metastatic breast cancer occurs when there is spread of the cancer outside the breast and regional node areas; this may occur despite adjuvant systemic therapy having been given. Once breast cancer becomes metastatic, it is no longer curable but is treatable, the aim of further treatment being to improve quality and length of life.

It has been shown that endocrine therapy improves survival in early breast cancer. Breast cancer cells that are endocrine‐dependent need oestrogen to proliferate. Early methods of hormonal therapy consisted of endocrine organ ablation by surgery Beatson 1896 but these procedures have been largely superseded by effective hormonal treatments. The most important single characteristic predicting response to hormone therapy is the original tumour receptor status EBCTG 1998. A good initial response to endocrine treatment is an indication to continue, on relapse, with second and even third line endocrine therapy until the disease becomes hormone resistant Roseman 1997.

Most endocrine therapies either block the binding of oestrogen to its receptor or reduce serum and tumour concentrations of oestradiol. The most widely‐used endocrine therapy for treatment of hormone‐sensitive metastatic disease is tamoxifen Howell 1997. Tamoxifen is an oral, non‐steroidal, competitive oestrogen receptor antagonist. However it also has an agonist effect; patients may relapse and develop acquired resistance to tamoxifen, although they may still respond to further different endocrine therapy .

In postmenopausal, women androgens (mainly from the adrenal glands) are converted into oestrogens in peripheral tissue by the enzyme aromatase Miller 1996. Aromatase inhibitors are a class of compounds that act systemically to inhibit oestrogen synthesis in tissues. Aromatase inhibitors are of two types, reversible and irreversible; both types of inhibitors compete with normal substrates for binding on the enzyme. The non‐competitive inhibitors (all steroidal) leave the enzyme permanently inactivated Ibrahim 1995.

Aminoglutethimide was the first generation aromatase inhibitor and although effective, it was poorly tolerated and was supplanted by the well‐tolerated second generation steroidal aromatase inhibitor 4‐OH‐androstenedione (formestane). Third generation aromatase inhibitors fall into two principal categories (a) non‐steroidal, reversible (triazole derivatives fadrozole, vorozole, letrozole, anastrazole) and (b) steroidal, irreversible (exemestane).

There is no evidence that any of the inhibitors differentially inhibit aromatase in different tissues and their role in premenopausal patients and in early breast cancer is still be elucidated.