Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial

G. Viale, M. M. Regan, P. Dell'Orto, M. G. Mastropasqua, E. Maiorano, B. B. Rasmussen, G. MacGrogan, J. F. Forbes, R. J. Paridaens, M. Colleoni, I. Láng, B. Thürlimann, H. Mouridsen, L. Mauriac, R. D. Gelber, K. N. Price, A. Goldhirsch, B. A. Gusterson, A. S. Coates

Research output: Contribution to journalArticle


Background: On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy forpostmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aromatase inhibitorsmaybe more or less important. Patients and methods: Breast International Group 1-98 trial randomized 6182 women among four groups comparing letrozole and tamoxifen with sequences of each agent; 5177 (84%) had centrally confirmed estrogen receptor (ER) positivity. We assessed whether centrally determined ER, progesterone receptor (PgR), human epidermal growth factor receptor 2, and Ki-67 labeling index, alone or in combination with other prognostic features, predicted the magnitude of letrozole effectiveness compared with either sequence or tamoxifen monotherapy. Results: Individually, none of the markers significantly predicted differential treatment effects. Subpopulation treatment effect pattern plot analysis of a composite measure of prognostic risk revealed three patterns. Estimated 5-year disease-free survival for letrozole monotherapy, letrozole/tamoxifen, tamoxifen/letrozole, and tamoxifen monotherapy were 96%, 94%, 93%, and 94%, respectively, for patients at lowest risk; 90%, 91%, 93%, and 86%, respectively, for patients at intermediate risk; and 80%, 76%, 74%, and 69%, respectively, for patients at highest risk. Conclusion: A composite measure of risk informs treatment selection better than individual biomarkers and supports the choice of 5 years of letrozole for patients at highest risk for recurrence.

Original languageEnglish
Pages (from-to)2201-2207
Number of pages7
JournalAnnals of Oncology
Issue number10
Publication statusPublished - Oct 2011



  • Aromatase inhibitor
  • Breast cancer
  • Prognostic factor
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Viale, G., Regan, M. M., Dell'Orto, P., Mastropasqua, M. G., Maiorano, E., Rasmussen, B. B., MacGrogan, G., Forbes, J. F., Paridaens, R. J., Colleoni, M., Láng, I., Thürlimann, B., Mouridsen, H., Mauriac, L., Gelber, R. D., Price, K. N., Goldhirsch, A., Gusterson, B. A., & Coates, A. S. (2011). Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Annals of Oncology, 22(10), 2201-2207. https://doi.org/10.1093/annonc/mdq738