Recent advances in endocrine therapy of breast cancer

Regression of advanced breast cancer as a result of endocrine therapy was first described over 100 years ago.1 Interest in this form of treatment increased when treatment with the antioestrogen tamoxifen after surgery for breast cancer was shown to improve patients' survival.2 3 Treatment also reduced the incidence of new cancers in the contralateral breast, which has led to a number of trials of tamoxifen as a preventive measure in women at high risk.4 New, potentially more active endocrine agents are now being introduced into clinical practice. In this review we outline the mechanism of action of these treatments and summarise recent results of clinical trials assessing their efficacy in comparison with older drugs; we also speculate about future trends in endocrine therapy and summarise clinical trials in progress. This article is based, in part, on our own collaborative experimental work and close association with pharmaceutical companies developing new endocrine agents. Additional reviews and original articles were obtained from searches of oncological journals. Recent data were obtained from presentations at the May meeting of the American Society for Clinical Oncology. #### Summary points Many new hormonal therapies that either antagonise oestrogen (antioestrogens) or inhibit its synthesis (aromatase inhibitors) are under intense clinical study Phase III trials including nearly 3000 patients have shown that new aromatase inhibitors have better tolerability and improved efficacy, including survival gains, than the other second line endocrine agents, megestrol acetate and aminoglutethimide New antioestrogens have less agonist activity than tamoxifen; it is not yet known if this will translate to important clinical gains Trials involving many thousands of breast cancer patients are under way to compare these exciting new agents with tamoxifen as first line therapy, both as adjuvant treatment and for advanced disease Breast cancer cells that are endocrine dependent need oestrogen to proliferate.5 …