title: Development of aromatase inhibitors and their pharmacologic profile.
abstract: 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.
authors.affiliation: Haukeland Hospital, Section of Oncology, Department of Medicine, University of Bergen, Bergen, Norway.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatnager
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole