A Comparison of Letrozole and Tamoxifen in Postmenopausal Women With Early Breast Cancer

N Engl J Med. 2005 Dec 29;353(26):2747-57. doi: 10.1056/NEJMoa052258.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.)

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Letrozole
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Second Primary / epidemiology
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Postmenopause
  • Proportional Hazards Models
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Secondary Prevention
  • Survival Rate
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use*
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Tamoxifen
  • Letrozole

Associated data

  • ClinicalTrials.gov/NCT00004205