Authors' objectives:

This report is intended to assess the usefulness of aromatase inhibitors (AIs) as adjuvant systematic therapy in postmenopausal women with early hormone-sensitive breast cancer.

Authors' results and conclusions: 12 reviews, 7 randomized clinical trials, 3 pharmacoeconomic studies and position statements papers issued by international oncology associations were selected for this report. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study which recruited more than 9,000 postmenopausal women reports that anastrozole showed a relative risk of 0.83 (CI 95% 0.73-0.94) as compared with tamoxifen for disease-free survival. This study has a follow-up of 68 months. The difference in absolute risk was 2.4% for the abovementioned result in favor of anastrozole. According to the Breast International Group (BIG) 01-98 study, at a 26 month follow-up median letrozole showed significantly longer disease-free survival (RR 0.81; 95% CI 0.70-0.93) and longer time to recurrence when compared to tamoxifen, though the magnitude of the absolute difference was small. Additionally, the MA-17 study showed that letrozole also offers minor but statistically significant advantages in extended therapy, i.e., beyond 5 years of adjuvant therapy. The International Examestate Study (IES) included 4,742 women who received examestane or tamoxifen after 2-3 years with adjuvant tamoxifen. After a 31 month follow-up median, the absolute difference favoring AIs for disease-free survival was 4.7%, with no changes in global survival. Adverse effects and limitants to clinical use: Toxicity profiles for the three more studied AIs: anastrazole, letrozole and examestane are similar. In general, they are associated to higher rates of hot flushes, arthralgia, myalgias, osteoporosis and bone fractures and with a lower rate of vaginal bleeding and thromboembolic events than with placebo. They do not present the harmful effects on the endometrium which tamoxifen has.

Authors' recommendations: In randomized clinical trials, AIs have proved their efficacy in adjuvant therapy for postmenopausal women with positive-receptor tumors. They seem to have a slightly higher efficacy, which is statistically significant, but clinically small. Anastrozole has been shown to improve disease-free survival when compared to tamoxifen; letrozole reduced the rate of events during extended adjuvant therapy and was at least as beneficial as tamoxifen during the first 5 years and examestane showed to improve disease-free survival when it replaced tamoxifen after 2-3 years of adjuvant therapy. Most clinical trials had relatively short follow-up periods. Generally, these drugs are well tolerated. Their most frequent side effects were hot flushes, myalgias, arthralgias and bone fractures secondary to osteoporosis. Their adverse effect profiles after 5 years of use remain unknown. European and Australian agencies recommend the use of AIs as an alternative to tamoxifen. The American Society of Clinical Oncology recommends the use of AIS initially for adjuvant therapy in early breast cancer. It suggests an aromatase inhibitor should be included at the beginning as treatment of choice or after 2-3 years with tamoxifen.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)