TY - JOUR
T1 - Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial
AU - Viale, G.
AU - Regan, M. M.
AU - Dell'Orto, P.
AU - Mastropasqua, M. G.
AU - Maiorano, E.
AU - Rasmussen, B. B.
AU - MacGrogan, G.
AU - Forbes, J. F.
AU - Paridaens, R. J.
AU - Colleoni, M.
AU - Láng, I.
AU - Thürlimann, B.
AU - Mouridsen, H.
AU - Mauriac, L.
AU - Gelber, R. D.
AU - Price, K. N.
AU - Goldhirsch, A.
AU - Gusterson, B. A.
AU - Coates, A. S.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Aromatase inhibitor
KW - Breast cancer
KW - Prognostic factor
KW - Tamoxifen
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U2 - 10.1093/annonc/mdq738
DO - 10.1093/annonc/mdq738
M3 - Article
C2 - 21335417
AN - SCOPUS:79959884829
VL - 22
SP - 2201
EP - 2207
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 10
ER -