Long-term toxicities of selective estrogen-receptor modulators and antiaromatase agents

Published literature indicates that the selective estrogen-receptor modulators (SERMs) tamoxifen and raloxifene (Evista) have favorable effects on bone density, lipid profiles, and the incidence of second breast cancers, and unfavorable effects on the incidence of venous thrombosis and hot flushes. Tamoxifen increases the risk of endometrial cancer, but raloxifene does not. The effects of SERMs on sexual function and cognition are unclear. Because the selective antiaromatase agents are relatively new, the long-term effects of these agents on normal tissues are less well established. It appears that the nonsteroidal agents (anastrozole [Arimidex], letrozole [Femara]) and steroidal (exemestane [Aromasin]) antiaromatase agents may have different effects on normal tissues. Preliminary data demonstrate that anastrozole increases the risk of arthralgias and produces a decrease in bone density. In contrast, exemestane appears to favorably affect bone density and lipid profile, similar to tamoxifen and raloxifene. The incidence of contralateral breast cancer is decreased in women on adjuvant anastrozole, but data for the other antiaromatase agents are not yet available. Hot flushes have been reported with the use of selective aromatase inhibitors, but their incidence seems to be comparable to what is reported with SERMs. Antiaromatase agents do not appear to cause venous thrombosis. More information about the effects of the antiaromatase agents on normal tissue will become available as data from ongoing adjuvant and chemoprevention trials are reported. Clinically, we should be conscious of the differences between antiaromatase agents and SERMs and their impact on women's health.