Estrogens play a pivotal role in the development of breast cancer. Endocrine therapy based on estrogen blockade is a well-established treatment in hormone-dependent breast cancer. Tamoxifen citrate has long been considered the "gold standard" due to its relative safety and efficacy. Aromatase inhibitors are anti-estrogen agents that target specifically the aromatase enzyme, which is the final step in the estrogen production. The first use of aromatase inhibitors in breast cancer was associated with adverse effects such as rash, drowsiness, and adrenal-gland suppression. Newer third-generation agents are emerging as potential alternatives to tamoxifen, associating clinical efficacy with a more favorable safety profile. The aim of this article is to review the mechanisms of actions pharmacology, adverse effects, and clinical applications of the aromatase inhibitors available in the United States. The terms breast cancer or neoplasia, aromatase, aromatase inhibitors, third-generation, endocrine therapy, and antiestrogens were used to search MEDLINE for English-language studies published between 1966 and April 2004. A parallel search was performed at the corresponding Web site of each of the aromatase inhibitors available in the United States. Identified publications relevant to the article objectives were selected. Anastrozole, letrozole, and exemestane are the 3 commercially available aromatase inhibitors approved by the US Food and Drug Administration for the treatment of hormone receptor-positive breast cancer in postmenopausal women. They have been used in several clinical scenarios, including advanced and early disease and chemoprevention, and in the neoadjuvant setting. There is evidence that aromatase inhibitors are more effective and tolerable than tamoxifen in advanced breast cancer and in the neoadjuvant setting. Based on the results of a large, randomized trial, their use in early disease and in chemoprevention is also promising. Aromatase inhibitors appear safe; however, the long-term safety profile is still unknown, especially concerning bone metabolism. Third-generation aromatase inhibitors are a new treatment modality in estrogen and/or progesterone-receptor positive breast cancer. Although they are replacing the "classic" antiestrogen agents used in metastatic breast cancer, their benefit in early disease and as chemopreventive agents is not completely clear. Ongoing clinical studies should become available within the next few years and will provide additional recommendations for their use in patients with breast cancer.
Choueiri, T. K., Alemany, C. A., Abou-Jawde, R. M., & Budd, G. T. (2004). Role of aromatase inhibitors in the treatment of breast cancer. Clinical Therapeutics, 26(8), 1199–1214. https://doi.org/10.1016/S0149-2918(04)80017-1