Safety of adjuvant aromatase inhibitor therapy

The long-term effects of aromatase inhibitors (AIs) on lipids and bone and cardiovascular and gynecological health are of particular interest to clinicians. The safety data of anastrozole, letrozole, and exemestane are limited to trials with follow-up periods of 5 years or less, and much of the data arise from comparisons with tamoxifen, a drug that has both estrogen agonist and antagonist effects. With the lack of extensive long-term data, indirect comparisons between the safety profiles of the AIs provide some insights. Although results from these indirect comparisons should be interpreted cautiously, they may assist physicians in the decision-making process. Thus far, AIs confer an increased risk of bone loss and osteoporosis and fractures, while the effects on lipid profiles and cardiovascular health seem to indicate only that AIs lack the cardioprotective and lipid-lowering effects of tamoxifen. Some data also are available from comparisons with placebo, a more appropriate comparator to investigate the tolerability and safety of a specific drug. In the MA.17 trial, patients receiving letrozole experienced similar rates of cardiovascular ischemic events and hypercholesterolemia compared with those on placebo. The significant clinical benefits of AIs compared with tamoxifen have been achieved without worsening quality of life.