Endocrine effects of aromatase inhibitors as adjuvant treatment in postmenopausal breast cancer patients

Aromatase inhibitors (AI) have become a cornerstone of adjuvant treatment for postmenopausal patients with estrogen receptor (ER)- positive early breast cancer. This chapter reviews the available evidence on endocrine effects of AI. Pharmacological activity of AI produces estradiol suppression, which represents the only known mechanism of action of such drugs, determining both side effects and antineoplastic efficacy. Overall, all third-generation AI (anastrozole, exemestane, letrozole) produce a significant suppression of estradiol levels, but there are some data suggesting that this effect might be less extensive than commonly thought and there are few comparative data to verify whether estradiol suppression varies with different AI. The most frequent side effects, related to estradiol suppression and reported in largescale clinical trials of adjuvant treatment with AI, are gynecological symptoms (less frequent and less severe than with tamoxifen, with the exception of vaginal dryness) and musculoskeletal symptoms (worse than with tamoxifen, which even has a positive effect on bone health). Disorders of lipid metabolism and cardiovascular side effects are less frequent. Among the latter, thromboembolism is less frequent with AI than with tamoxifen. There are many issues still of interest for clinical research on endocrine effects of AI. For example, it seems of utmost importance to verify whether endocrine effects might be predictive of AI efficacy and help to select the patients who can derive the greatest benefit from treatment with these drugs