Aromatase inhibitors (AIs) have become the first-choice endocrine drugs for postmenopausal breast cancer patients since they are associated with superior activity and better general tolerability when compared with tamoxifen both in the adjuvant and metastatic settings. As a consequence, the question is no more if a postmenopausal patient should have AIs as part of her adjuvant treatment, but when should it be started or which one should be preferentially used. Newer compounds, generally defined as third-generation AIs, are biochemically more selective and potent when compared with older ones, and they also show superior clinical activity. As yet, no large randomised study has been published comparing the three third-generation AIs on the market. Nevertheless, both laboratory and clinical data suggest that the steroidal (exemestane) and non-steroidal (anastrozole, letrozole) AIs may have slightly different toxicity profiles, probably due to the low androgenic action of the formers. While waiting for randomised data on clinical efficacy of third-generation AIs, such differences may help select the best drug in elderly patients with a low cumulative risk of relapse and a significant amount of co-morbidities, such as cardiovascular disease or osteoporosis.
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