The Efficacy of 3rd Generation Aromatase Inhibitors in Breast Cancer Chemoprevention

Background: Currently, tamoxifen and raloxifene are the only FDA-approved and USPSTF recommended pharmacologic treatments for breast cancer chemoprevention in high-risk postmenopausal women. Despite their widely recognized efficacy at reducing the incidence of breast cancer, the risk of potentially significant adverse effects may limit patient allocation. Consequently, research on the efficacy of third-generation aromatase inhibitors (AIs) as breast cancer preventives has emerged, especially since their value as adjuvant and combination therapy for breast cancer is well-established. The safety profile of anastrozole and exemestane potentially provide an appealing alternative to postmenopausal patients with a higher risk of developing breast cancer. Studies have successfully demonstrated the efficacy of AIs at reducing the incidence breast cancer, and further research will help to validate the FDA-approval of AIs for this indication. Methods: An exhaustive search of medical literature included MEDLINE, Web of Science, CINAHL, and the National Institute of Health Clinical Trials using the key words: aromatase inhibitors, anastrozole, letrozole, exemestane, and chemoprevention. Relevant articles were critically appraised and GRADE was used for qualitative assessment. Results: An extensive literary search rendered 262 relevant articles from January 2000 to February 2014. After screening several articles, two randomized control trials met inclusion criteria. The NIH clinical trials site yielded 36 results, and one trial met inclusion criteria. The LIBER trial, listed under NCT00673335, is in Phase III with a predicted completion date of February 2017. Conclusion: Third generation AIs, such as anastrozole and exemestane, are very effective at reducing the incidence of invasive breast cancer, ductal carcinoma in situ, and certain tumors in high-risk postmenopausal women. Although both AIs demonstrate adverse effects, their overall safety profiles may be more favorable than other pharmacologic chemoprevention alternatives. More research, larger scale studies, and a longer follow-up after concluding treatment will be valuable to the prospective FDA-approval of AIs in breast cancer prevention. Keywords: aromatase inhibitors, anastrozole, letrozole, exemestane, chemopreventio