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.

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; for the BIG 1-98 Collaborative and International Breast Cancer Study Groups. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 22:10(2011 Oct), pp. 2201-2207. [10.1093/annonc/mdq738]

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
Primo
;
2011

Abstract

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.
Aromatase inhibitor; Breast cancer; Prognostic factor; Tamoxifen
Settore MED/08 - Anatomia Patologica
ott-2011
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/162230
Citazioni
  • ???jsp.display-item.citation.pmc??? 30
  • Scopus 89
  • ???jsp.display-item.citation.isi??? 74
social impact