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

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.

• Authors: 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, BIG 1-98 Collaborative and International Breast Cancer Study Groups
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 22 Issue 10 Pg. 2201-7 (Oct 2011) ISSN: 1569-8041 [Electronic] England
• PMID: 21335417 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aromatase Inhibitors
• Ki-67 Antigen
• Nitriles
• Receptors, Estrogen
• Receptors, Progesterone
• Triazoles
• Tamoxifen
• Letrozole
• ErbB Receptors

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Aromatase Inhibitors (administration & dosage)
• Breast Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Chemotherapy, Adjuvant
• Double-Blind Method
• Drug Administration Schedule
• ErbB Receptors (biosynthesis)
• Female
• Humans
• Ki-67 Antigen (biosynthesis)
• Letrozole
• Middle Aged
• Nitriles (administration & dosage)
• Prognosis
• Receptors, Estrogen (biosynthesis)
• Receptors, Progesterone (biosynthesis)
• Tamoxifen (administration & dosage)
• Triazoles (administration & dosage)