Aromatase inhibitors (AIs) are approved for use in both early and advanced-stage breast cancer in postmenopausal women. Although the currently approved “third-generation” AIs all powerfully inhibit estrogen synthesis, they may be subdivided into steroidal and nonsteroidal inhibitors, which interact with the aromatase enzyme differently. Nonsteroidal AIs bind non- covalently and reversibly to the aromatase protein, whereas steroidal AIs may bind covalently and irreversibly to the aromatase enzyme.
Although both steroidal and nonsteroidal AIs block aromatase activity, there are distinct differences between the classes. The differences relate to the type of binding to the aromatase enzyme (irreversible or reversible binding for steroidal or nonsteroidal AIs, respectively) and potential androgenic effects of exemestane, which may exert additional effects. Based on preclinical and clinical studies , there does not appear to be an advantage in combining the SERM tamoxifen with a nonsteroidal AI as initial therapy. However, preclinical findings suggest that there is an advantage in combining tamoxifen with steroidal AIs.
The Oncologist 2008;13:829 – 837