Authors' objectives:

This report is intended to review extended adjuvant treatment with letrozole in breast cancer after 5 years of tamoxifen therapy.

Authors' results and conclusions: 7 non systematic revisions, 3 controlled clinical trials, 2 cost-effectiveness studies and documents stating the FDA and the American Society of Clinical Oncology's point of view were identified, Treatment with letrozole significantly improved disease-free survival in a double-blind, multicenter, placebo-controlled concomitant radiochemotherapy (CRCT), the MA-17, which included postmenopausal women with positive hormone receptors who had received five years of tamoxifen in early breast cancer. After a mean follow-up of 2.4 years, the disease-free survival rate for letrozole and placebo were 93% and 87%, respectively. The relative risk for local or metastasic recurrence or for a new contralateral neoplasia in the letrozole group as compared to the placebo group was 0.57 (CI 95%) 0.43-0.75; p<0.001. The global benefit is 43% risk reduction for recurrence or new contralateral cancer being this an absolute risk difference of 2.2% vs placebo at less than three years follow-up. The American Society of Oncology recommends that postmenopausal women completing 5 year tamoxifen therapy with early hormone-sensitive breast cancer should be considered for letrozole therapy. A minimum of 2.5 year treatment is recommended. Adverse and limiting effects of its use: Adverse effects are uncommon, <1%. Flushing, arthralgia, myalgia and arthritis. In general, the adverse effect profile is similar to that of tamoxifen. Less vaginal bleeding was reported. In addition, an increase in new diagnoses of osteoporosis was evidenced.

Authors' recommendations: All women should be considered for extendend adjuvant treatment, including those initially considered as minimum risk. In the MA-17 trial, letrozole has proved to be efficient in extended adjuvant treatment, thus providing a statistically significant extension in disease-free survival. Fractures and cardiovascular events were similar to those from the placebo group. There was an increase in the number of new osteoporosis diagnoses. Letrozole is currently apporoved for extended adjuvant treatment in postmenopausal women with early breast cancer who have received tamoxifen for 5 years. The effect observed cannot be considered a class effect and recomendation for extended treatment is assessed for letrozole only. However, due to the fact that the treatment and follow-up in the identified clinical trials are short, it is impossible to determine its long-term efficacy and tolerability profile. There are also controversies as regards its effect on bone metabolism. Under these circumstances, both professionals and patients should jointly consider the residual risk of recurrence and individual preferences after completing 2 years and a half with letrozole. Pharmaceutical and economic assessments under way on the cost-effectiveness of letrozole in extended adjuvant treatment are expected.

Authors' methods: Overview

Project Status: Completed

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

Year Published: 2005

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)