Indications and limitations of third-gene ration aromatase inhibitors

Background: Use of aromatase inhibitors in postmenopausal breast cancer, initially in advanced disease but recently also for adjuvant therapy, represents a major advance. Objective: To summarize research leading to this success and to review clinical data from large Phase III trials revealing efficacy of novel third-generation aromatase inhibitors in metastatic and early breast cancer. Methods: Literature on PubMed and on ISI Web of Science for the last 10 years was searched using the word 'aromatase'. Recent key presentations and abstracts are also included. Results/conclusion: Third-generation aromatase inhibitors improve relapse-free survival compared to tamoxifen, and some trials reveal a survival advantage in early breast cancer. Although substantial data now confirm the safety of these potent compounds with respect to bone metabolism and cardiovascular risk, there is a need for continuous long-term follow-up, in particular into potential vascular effects. The mechanisms and optimal treatment of musculoskeletal and joint pain remain to be addressed. Ongoing studies evaluate sequential treatment versus monotherapy, potential differences between individual compounds and optimal duration of treatment, as well as combining aromatase inhibitors with novel targeting agents.