Biological rationale for endocrine therapy in breast cancer.

Oestrogens are heavily implicated in the risk to, and progression of, breast cancer. Therapeutic strategies targeted at the oestrogenic stimulus to the breast and hormone-sensitive breast cancers are extremely attractive measures both to prevent the disease and to treat established tumours. The present review outlines the biological rationale for such endocrine therapy and traces the evolution whereby irreversible surgical procedures have been replaced by potent and specific drugs. In particular, the development of the latest generation of agents which inhibit oestrogen biosynthesis (aromatase inhibitors) is considered by defining the central role of the aromatase enzyme, its regulation and contribution to circulating and tumour endogenous oestrogens. The nature of response and resistance which may be elicited following the use of endocrine therapy is also described as this may determine the optimal use of aromatase inhibitors and, more generally, anti-hormone therapy in the management of women at high risk to, or with, breast cancer.