Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: The BIG 1-98 trial

Diana Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N. Price, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert J. Paridaens, Monica Castiglione-Gertsch, Richard D. Gelber, Marco Colleoni, István Láng, Lucia Del Mastro, Laurence Gladieff, Manuela Rabaglio, Ian E. Smith, Jacquie H. Chirgwin, Aron Goldhirsch

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Purpose: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. Methods: This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295). Results: Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs. Conclusion: Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.

Original languageEnglish
Pages (from-to)1972-1979
Number of pages8
JournalJournal of Clinical Oncology
Issue number12
Publication statusPublished - jan. 1 2008


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Crivellari, D., Sun, Z., Coates, A. S., Price, K. N., Thürlimann, B., Mouridsen, H., Mauriac, L., Forbes, J. F., Paridaens, R. J., Castiglione-Gertsch, M., Gelber, R. D., Colleoni, M., Láng, I., Del Mastro, L., Gladieff, L., Rabaglio, M., Smith, I. E., Chirgwin, J. H., & Goldhirsch, A. (2008). Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: The BIG 1-98 trial. Journal of Clinical Oncology, 26(12), 1972-1979. https://doi.org/10.1200/JCO.2007.14.0459