Aromatase inhibitors in the management of early breast cancer: optimizing the clinical benefit.

Several adjuvant trials evaluating aromatase inhibitors in postmenopausal women with early breast cancer have shown significant improvement upon, or extension of the efficacy benefits of, standard therapy with tamoxifen, and treatments were generally well tolerated. Disease-free survival was significantly improved by: anastrozole versus tamoxifen for 5 years of adjuvant therapy, in the Arimidex, Tamoxifen Alone or in Combination trial; switching to exemestane after 2 to 3 years of tamoxifen, compared with remaining on tamoxifen for 5 years, in the Intergroup Exemestane Study; and switching to letrozole (v placebo) for 5 years after 5 years of tamoxifen, in the extended adjuvant trial, MA.17. Further analyses of these trials, and data from ongoing trials, will address how to optimally use aromatase inhibitors in the adjuvant breast cancer setting: whether these agents should be used in place of, or sequenced with, tamoxifen; what is the best order of sequencing, before or after tamoxifen, and when is the best time to switch; what the long-term safety issues are associated with aromatase inhibitor treatment; and how toxicities can be effectively managed.