Authors: Agustí Barnadas Laura G Estévez Ana LluchHernández Álvaro RodriguezLescure César RodriguezSanchez Pedro SanchezRovira
Publish Date: 2011/11/07
Volume: 28, Issue: 12, Pages: 1045-1058
Abstract
Thirdgeneration aromatase inhibitors AIs have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor HR positive HR+ status and nowadays are used in the adjuvant and neoadjuvant settings and firstline therapy for advanced breast cancer Letrozole is a third generation AI as are anastrozole and exemestane In the past clinical studies had demonstrated that letrozole was effective as a secondline treatment of metastatic breast cancer In this paper pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings Additionally the results of important clinical trials such as Breast International Group BIG 198 which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen MA17 that evaluates the benefits of extended adjuvant therapy and other important studies in advanced and neoadjuvant disease are reviewed Safety comparisons of treatments are also addressed Interestingly about 50 of human epidermal growth factor receptor 2positive HER2+ breast cancers are HR+ However HER2 positivity is a marker of antiestrogen treatment resistance Because of this a dual treatment is a logical approach when both receptors are overexpressed The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome Also the combination of everolimus plus letrozole has been tested in this setting In fact the coadministration of both agents seems to increase the efficacy of letrozole in newlydiagnosed HR+ patients Once resistance to sequential trastuzumab and AI as monotherapy has been found trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents according to recently reported results
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