Incidence and management of side effects associated with aromatase inhibitors in the adjuvant treatment of breast cancer in postmenopausal women

Objective: Third-generation aromatase inhibitors (AIs) are effective and generally well-tolerated as adjuvant therapy. These AIs are now being introduced for the adjuvant treatment of postmenopausal patients with estrogen-receptor-positive early-stage breast cancer. However, questions remain about their long-term safety. This paper summarizes the adverse events reported in third-generation AI trials and comments on the appropriate management of these drug-induced adverse events in patients. Methods: Papers relating to anastrozole, exemestane, and letrozole were identified through Medline searches, and proceedings of recent oncology meetings were also reviewed to capture relevant emerging data. Results: The most commonly reported adverse events associated with adjuvant AI therapy include hot flushes and musculoskeletal complaints/arthralgia. The incidence of endometrial cancer and thromboembolic events is significantly lower with an AI than with tamoxifen. However, there is a small but significant increase in the risk of osteoporosis and fractures with AI therapy. A potential negative effect on the cardiovascular system, specifically on lipid metabolism, has not been conclusively demonstrated. No significant differences in overall quality of life were observed in studies comparing AIs with tamoxifen or placebo. Conclusion: AIs alone and sequenced after tamoxifen are an appropriate option for adjuvant endocrine therapy for most postmenopausal patients with hormone-responsive breast cancer. The incidence of some side effects such as endometrial cancer, stroke, or pulmonary embolism associated with tamoxifen is decreased. Monitoring and management of bone loss associated with AI treatment are essential and are being addressed in ongoing trials. Further studies with longer follow- up are required to clarify the effects of AIs on lipid metabolism and cardiovascular health.