In randomized clinical trials, AIs have proved their efficacy in adjuvant therapy for postmenopausal women with positive-receptor tumors. They seem to have a slightly higher efficacy, which is statistically significant, but clinically small.
Anastrozole has been shown to improve disease-free survival when compared to tamoxifen; letrozole reduced the rate of events during extended adjuvant therapy and was at least as beneficial as tamoxifen during the first 5 years and examestane showed to improve disease-free survival when it replaced tamoxifen after 2-3 years of adjuvant therapy. Most clinical trials had relatively short follow-up periods. Generally, these drugs are well tolerated. Their most frequent side effects were hot flushes, myalgias, arthralgias and bone fractures secondary to osteoporosis. Their adverse effect profiles after 5 years of use remain unknown. European and Australian agencies recommend the use of AIs as an alternative to tamoxifen. The American Society of Clinical Oncology recommends the use of AIS initially for adjuvant therapy in early breast cancer. It suggests an aromatase inhibitor should be included at the beginning as treatment of choice or after 2-3 years with tamoxifen.