Use of aromatase inhibitors in breast carcinoma

Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of andro gens to estrogens, is the major mechanism of estrogen synthesis in the post -menopausal woman. We review some of the recent scientific advances which s hed light on the biologic significance, physiology, expression and regulati on of aromatase in breast tissue. Inhibition of aromatase, the terminal ste p in estrogen biosynthesis, provides a way of treating hormone-dependent br east cancer in older patients. Aminoglutethimide was the first widely used aromatase inhibitor but had several clinical drawbacks. Newer agents are co nsiderably more selective, more potent, less toxic and easier to use in the clinical setting. This article reviews the clinical data supporting the us e of the potent, oral competitive aromatase inhibitors anastrozole, letrozo le and vorozole and the irreversible inhibitors 4-OH androstenedione and ex emestane. The more potent compounds inhibit both peripheral and intra-tumor al aromatase. We discuss the evidence supporting the notion that aromatase inhibitors lack cross-resistance with antiestrogens and suggest that the ne wer, more potent compounds may have a particular application in breast canc er treatment in a setting of adaptive hypersensitivity to estrogens. Curren tly available aromatase inhibitors are safe and effective in the management of hormone-dependent breast cancer in post-menopausal women failing anties trogen therapy and should now be used before progestational agents. There i s abundant evidence to support testing these compounds as first-line hormon al therapy for metastatic breast cancer as well as part of adjuvant regimen s in older patients and quite possibly in chemoprevention trials of breast cancer.