title: A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.
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.)
authors.affiliation: Senology Center of Eastern Switzerland, Kantonsspital, St. Gallen, and the Swiss Group for Clinical Cancer Research, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Thürlimann
authors.forename: Aparna
authors.initials: A
authors.lastname: Keshaviah
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Henning
authors.initials: H
authors.lastname: Mouridsen
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.forename: John F
authors.initials: JF
authors.lastname: Forbes
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Manuela
authors.initials: M
authors.lastname: Rabaglio
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardley
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardly
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D055502:Secondary Prevention; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole