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.