Tamoxifen (Novaldex) provides a survival benefit to women with hormone receptor-positive breast cancer when given for 5 years, but not when given for a longer period.
Letrozole (Femara) is an estrogen synthetase inhibitor, and has been shown to be effective in patients taking tamoxifen who nonetheless have metastatic disease.
In this trial, women (n=5,187) were included if they had completed a 5-year course of tamoxifen, had a life expectancy of at least 5 years and were either postmenopausal or older than 50 years. Approximately half were axillary node-negative. Allocation concealment and blinding were not described, and the study was partly funded by the manufacturer. Analysis was by intention to treat, and the study was halted prematurely once letrozole demonstrated an advantage.
Patients were followed up for a median of 2.4 years. Patients receiving letrozole had a better disease-free survival than those receiving placebo (93% vs 87%; p=0.008; adjusted risk ratio=6; number-needed-to-treat= 16). There was a trend towards better overall survival in the letrozole group (96% vs 93.6%), but this was not statistically significant.
Patients taking letrozole were more likely to experience hot flashes (47.2% vs 40.5%), arthritis (5.6% vs 3.5%) and arthralgia (21.3% vs 16.6%), but were slightly less likely to experience vaginal bleeding (4.3% vs 6.0%).
For women with hormone-dependent breast cancer, letrozole given after a 5-year course of tamoxifen increases disease-free survival and is generally well tolerated.
(Level of evidence = 1b)
Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.
N Engl J Med 2003;349:1793-802.