Comparative review of anastrozole, letrozole and exemestane in the management of early breast cancer.
The hormonal therapy of patients with endocrine-sensitive early breast cancer has mainly consisted, for several decades, of the gold standard tamoxifen. The efficacy and favorable toxicity profiles of third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, in advanced disease led to their development in early breast cancer. Recent results consistently show the superiority of these agents over tamoxifen. Adjuvant trials evaluated AIs using four different therapeutic approaches: (1) Upfront strategy: randomization of newly diagnosed patients: tamoxifen for 5 years versus AI for 5 years. (2) Sequencial strategy: randomization of newly diagnosed patients: tamoxifen (2 - 3 years) followed by AI or the inverse for a total of 5 years versus upfront AI for 5 years. (3) Switch strategy: delayed randomization (or analysis) after 2 - 3 years of tamoxifen (patients free of disease): 2 - 3 years of tamoxifen versus 2 - 3 years of AI (total treatment 5 years). (4) Extended strategy: delayed randomization after 5 years of tamoxifen (patients free of disease): 2 - 5 years of AI versus placebo. Overall, AIs show evidence of superiority over tamoxifen in the adjuvant setting with proven improved efficacy and better toxicity profile. Despite some common characteristics, a body of evidence on AIs indicates some specific differences between the three agents in mechanism of action, pharmacokinetics, efficacy as well as toxicity profiles. Consequently, these hormonal agents may not be considered interchangeable in clinical practice. This review explores available results from AI trials and tries to define their present role in the adjuvant management of postmenopausal patients with breast cancer.
Nabholtz
Jean-Marc
JM
Jean Perrin Comprehensive Cancer Centre, Department of Medicine, 58, rue Montalembert, 63000 Clermont-Ferrand, France. jmnabholtz@cjp.com
Mouret-Reynier
Marie-Ange
MA
Durando
Xavier
X
Van Praagh
Isabelle
I
Al-Sukhun
Sana
S
Ferriere
Jean-Pierre
JP
Chollet
Philippe
P
D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D019468:Disease Management; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000639:trends; D014230:Triazoles / Q000627:therapeutic use*
D000730:Androstadienes; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane