Aromatase inhibitors in advanced breast cancer.
The third-generation aromatase inhibitors suppress whole-body estrogen production in postmenopausal women with high specificity and potency. In women with hormone-sensitive breast cancer, three of these agents, letrozole, anastrozole, and exemestane, provide an important alternative endocrine therapy to the antiestrogen tamoxifen, which blocks estrogen activation of the estrogen receptor. For treatment of advanced or metastatic breast cancer that has progressed on first-line tamoxifen, all three agents are active. On that basis, they have each been compared with tamoxifen as first-line therapy of advanced breast cancer, in phase III trials. Letrozole was significantly superior to tamoxifen in the primary end point, median time to progression, as well as in response rate and clinical benefit rate, and treatment was well tolerated. Although there was no significant difference in median overall survival, an advantage seen with letrozole for the first 2 years may have been lost because of crossover to the alternate agent at disease progression. Anastrozole was evaluated in two separate trials designed for combined analysis. Overall, anastrozole was at least equivalent to tamoxifen in activity, but clearly superior only for median time to progression in the subgroup of patients with hormone receptor-positive disease. Treatment was generally as well tolerated as tamoxifen. In an early report, exemestane was significantly better than tamoxifen in response rate and median time to progression, with overall survival data not yet available. To date, letrozole appears to be the most effective aromatase inhibitor in the first-line advanced breast cancer setting.
Mouridsen
Henning T
HT
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D000077289:Letrozole; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000627:therapeutic use; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D014230:Triazoles / Q000627:therapeutic use
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane