The role of aromatase inhibitors in breast cancer.

Aminoglutethimide (AG) has antitumor activity in disseminated breast cancer similar to that of surgical adrenalectomy. AG works by blocking conversion of aromatase enzymes necessary for conversion of androgens to estrogens. Tumor response in patients with disseminated disease has been approximately 30%, with a further 13% of patients achieving stabilization of disease. Age and previous systemic treatment did not influence response to AG, except that those who had not responded to previous endocrine responded less well to AG. Relief of bone pain occurred not only in patients whose bone metastases objectively responded but also in some patients whose disease progressed. Side effects, although significant initially, usually subsided within 3 weeks; the incidence of side effects may be related to the rate of acetylation of the drug by the liver. In randomized clinical trials, AG has been shown to be as effective as adrenalectomy and tamoxifen therapy. AG was not as well tolerated as tamoxifen, but it was more effective in patients with bone metastases.