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

Publication

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

Journal Paper/Review - Feb 18, 2011

Viale G, Thürlimann Beat, Mouridsen H, Mauriac L, Gelber R D, Price K N, Goldhirsch A, Gusterson B A, Coates A S, Láng I, Colleoni M, Regan M M, Dell'orto P, Mastropasqua M G, Maiorano E, Rasmussen B B, Macgrogan G, Forbes J F, Paridaens R J, for the BIG 1-98 Collaborative and International Breast Cancer Study Groups

Citation

Viale G, Thürlimann B, Mouridsen H, Mauriac L, Gelber R, Price K, Goldhirsch A, Gusterson B, Coates A, Láng I, Colleoni M, Regan M, Dell'orto P, Mastropasqua M, Maiorano E, Rasmussen B, Macgrogan G, Forbes J, Paridaens R, for the BIG 1-98 Collaborative and International Breast Cancer Study Groups. Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol 2011; 22:2201-2207.

Type

Journal Paper/Review (English)

Journal

Ann Oncol 2011; 22

Publication Date

Feb 18, 2011

Issn Electronic

1569-8041

Pages

2201-2207

Brief description/objective

BACKGROUND: On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal 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 inhibitors may be 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.