Development of aromatase inhibitors and their pharmacologic profile

Major advances have been recently made in the treatment of postmenopausal women with hormone-sensitive breast cancer. It is widely accepted that estrogen is associated with the progression of hormone-sensitive breast cancer. Whereas previous therapy was based on surgical ablation (ovariectomy, adrenalectomy, and hypophysectomy) or additive treatment (estrogens, androgens), more recently antiestrogens (in premenopausal as well as postmenopausal women), medical ovarian ablation, and aromatase inhibition have replaced these procedures. The current focus of clinical research efforts is to maximize efficacy with these agents and determine an effective treatment strategy for these patients. This article reviews the development of aromatase inhibitors and inactivators (AIs), with particular emphasis on the potent third-generation agents now available. Also provided is information on the relative potency and efficiency of estrogen synthesis inhibition with these agents. Results from in vitro and in vivo studies of AIs suggest that there is variability in efficacy among agents in this class, and the potential clinical implications of these variations are discussed.