Publikation
Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial
Wissenschaftlicher Artikel/Review - 18.02.2011
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
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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.