Summary of aromatase inhibitor clinical trials in postmenopausal women with early breast cancer.

Five years of adjuvant therapy with tamoxifen was considered the gold-standard treatment for postmenopausal women with estrogen receptor-positive breast cancer for many years. Data from a core group of clinical trials investigating the safety and efficacy of aromatase inhibitors (AIs) have challenged this perception. These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98), 2) in a "switched setting" after 2 to 3 years of treatment with tamoxifen (Arimidex-Nolvadex 95, the Austrian Breast and Colorectal Cancer Study Group 8 [ABCSG 8] trial, the Italian Tamoxifen Anastrozole study, the Intergroup Exemestane Study), and 3) in extended settings (National Cancer Institute of Canada Trial MA.17, ABCSG 6a, National Surgical Adjuvant Breast and Bowel Project 33). The efficacy data from these studies suggested that AIs have added substantial benefit in terms of disease outcome. AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen. However, patients who received tamoxifen had less skeletal events and accelerated bone resorption compared with women who received AIs. AIs should be considered when planning a patient's endocrine therapy, taking into account the differences in tolerability and end-organ effects of the classes of endocrine therapy. Outstanding issues to optimize AI therapy include identifying the optimal duration, agent, and patients for these therapies.