[Commentary on] A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.

Tamoxifen, given for 5 years after surgery for hormone-dependent breast cancer, prolongs disease-free survival and overall survival. No added effect is noted with more than 5 years of treatment. This study, enrolling postmenopausal women who had been treated for early-stage breast cancer, was intended to show whether letrozole improves the outcome after tamoxifen therapy is withdrawn. Letrozole is an aromatase inhibitor that suppresses estrogen production. Using a randomized, double-blind design, 5187 women who had taken adjuvant tamoxifen therapy for 4.5 to 6 years were assigned to receive 2.5 mg letrozole or placebo orally each day for 5 years. All participants were age 50 and older when tamoxifen therapy began, and all had a tumor that was positive for estrogen receptors and/or progesterone receptors. After a median follow up of 2.4 years, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the other breast, 75 in the letrozole-treated group and 132 in placebo recipients. The estimated 4-year disease-free survival rates were 93% and 87%, respectively. The hazard ratio for cancer in the letrozole group was 0.57. Women with negative lymph nodes did at least as well as those with node-positive disease when given letrozole. Overall survival rates were 96% in the letrozole group and 94% in placebo patients, with a hazard ratio in the former group of 0.76. Hot flashes, arthritis/arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding occurred more often in the placebo group. Comparable numbers of patients (4.5% and 3.6%, respectively) discontinued treatment because of toxic effects. A trend was noted toward more frequent newly diagnosed osteoporosis in patients given letrozole. The investigators concluded that letrozole should be considered for postmenopausal women with hormone receptor-positive breast cancer who have completed 5 years of tamoxifen therapy. The optimal duration of letrozole treatment remains to be determined.