A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.

The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.)

Breast International Group (BIG) 1-98 Collaborative Group ，Thürlimann B ，Keshaviah A ，Coates AS ，Mouridsen H ，Mauriac L ，Forbes JF ，Paridaens R ，Castiglione-Gertsch M ，Gelber RD ，Rabaglio M ，Smith I ，Wardley A ，Price KN ，Goldhirsch A ... -  《-》

Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98.

Coates AS ，Keshaviah A ，Thürlimann B ，Mouridsen H ，Mauriac L ，Forbes JF ，Paridaens R ，Castiglione-Gertsch M ，Gelber RD ，Colleoni M ，Láng I ，Del Mastro L ，Smith I ，Chirgwin J ，Nogaret JM ，Pienkowski T ，Wardley A ，Jakobsen EH ，Price KN ，Goldhirsch A ... -  《-》

Update of the BIG 1-98 Trial: where do we stand?

Joerger M ，Thürlimann B 《-》

The use of early adjuvant aromatase inhibitor therapy: contributions from the BIG 1-98 letrozole trial.

Forbes JF 《SEMINARS IN ONCOLOGY》

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

In hormone-dependent breast cancer, five years of postoperative tamoxifen therapy--but not tamoxifen therapy of longer duration--prolongs disease-free and overall survival. The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy. We conducted a double-blind, placebo-controlled trial to test the effectiveness of five years of letrozole therapy in postmenopausal women with breast cancer who have completed five years of tamoxifen therapy. The primary end point was disease-free survival. A total of 5187 women were enrolled (median follow-up, 2.4 years). At the first interim analysis, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the contralateral breast--75 in the letrozole group and 132 in the placebo group--with estimated four-year disease-free survival rates of 93 percent and 87 percent, respectively, in the two groups (P< or =0.001 for the comparison of disease-free survival). A total of 42 women in the placebo group and 31 women in the letrozole group died (P=0.25 for the comparison of overall survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding was less frequent. There were new diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group and 4.5 percent of the women in the placebo group (P=0.07); the rates of fracture were similar. After the first interim analysis, the independent data and safety monitoring committee recommended termination of the trial and prompt communication of the results to the participants. As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival.

Goss PE ，Ingle JN ，Martino S ，Robert NJ ，Muss HB ，Piccart MJ ，Castiglione M ，Tu D ，Shepherd LE ，Pritchard KI ，Livingston RB ，Davidson NE ，Norton L ，Perez EA ，Abrams JS ，Therasse P ，Palmer MJ ，Pater JL ... -  《-》