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The use of third-generation aromatase inhibitors and tamoxifen in the adjuvant treatment of postmenopausal patients with hormone-dependent breast cancer: evidence based review

(1) Worldwide, breast cancer is the most common type of cancer in women, and the second most frequently diagnosed cancer overall. (2) Since its approval approximately 20 years ago, a 5-year course of tamoxifen has been the standard adjuvant therapy for patients with hormone-dependent breast cancer. (3) Recently, data from large randomised clinical trials have indicated that the third-generation aromatase inhibitors (letrozole, anastrozole and exemestane) are more effective than tamoxifen as adjuvant therapy in postmenopausal women with operable breast cancer when given either initially, or sequentially following initial tamoxifen therapy, within the first five years post-operatively. (4) One large randomised trial demonstrated that administration of letrozole to high-risk (node-positive) postmenopausal patients who have completed 5 years' adjuvant tamoxifen further prevents late recurrences and contralateral breast cancer, contrary to the lack of obvious benefit of extending tamoxifen treatment to 10 years found in another large randomised study. (5) Aromatase inhibitors and tamoxifen should not be administered concomitantly as this does not provide additional benefit, and a large, randomised study demonstrated reduced disease-free survival with the combination of anastrozole plus tamoxifen compared with anastrozole alone. (6) Further studies are required to establish whether the third-generation aromatase inhibitors prolong overall survival compared with tamoxifen, to evaluate their long-term efficacy and tolerability profiles, and to determine the optimal treatment duration with these agents.