TY - JOUR
T1 - Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor
T2 - National Cancer Institute of Canada Clinical Trials Group MA.17
AU - Goss, Paul E.
AU - Ingle, James N.
AU - Martino, Silvana
AU - Robert, Nicholas J.
AU - Muss, Hyman B.
AU - Piccart, Martine J.
AU - Castiglione, Monica
AU - Tu, Dongsheng
AU - Shepherd, Lois E.
AU - Pritchard, Kathleen I.
AU - Livingston, Robert B.
AU - Davidson, Nancy E.
AU - Norton, Larry
AU - Perez, Edith A.
AU - Abrams, Jeffrey S.
AU - Cameron, David A.
AU - Palmer, Michael J.
AU - Pater, Joseph L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/5/20
Y1 - 2007/5/20
N2 - Purpose: Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods: Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results: The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR- subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09). Conclusion: These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.
AB - Purpose: Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods: Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results: The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR- subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09). Conclusion: These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.
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U2 - 10.1200/JCO.2006.09.4482
DO - 10.1200/JCO.2006.09.4482
M3 - Article
C2 - 17452676
AN - SCOPUS:34249936011
SN - 0732-183X
VL - 25
SP - 2006
EP - 2011
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -