Sofia K. Gruvberger-Saal, Pär-Ola Bendahl, Lao H. Saal, Mervi Laakso, Cecilia Hegardt, Patrik Edén, Carsten Peterson, Per Malmström, Jorma Isola, Åke Borg and Mårten Fernö
Estrogen receptor beta predicts tamoxifen sensitivity for estrogen receptor alpha negative breast cancer
Clinical Cancer Research 13, 1987-1994 (2007)
Abstract:
Purpose: Endocrine therapies such as tamoxifen are commonly given to most patients with ERα- positive breast carcinoma but are not indicated for persons with ERα-negative cancer . The factors responsible for response to tamoxifen in 5-10% of patients with ERα-negative tumors are not clear. The aim of the present study was to elucidate the biology and role of the second ER, ERβ, in endocrine therapy response.
Experimental Design: We investigated ERβ by immunohistochemistry in 353 stage II primary breast tumors from patients treated with two years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.
Results: ERβ was associated with increased survival (distant disease-free survival, P=0.01; overall survival, P=0.22), and in particular within ERα-negative patients (P=0.003; P=0.04), but not in the ERα-positive subgroup (P=0.49; P=0.88). Lack of ERβ conferred early relapse (HR, 14; 95% CI, 1.8- 106; P=0.01) within the ERα-negative subgroup even after adjustment for other markers. ERα was a independent marker only within the ERβ-negative tumors (HR, 0.44; 95% CI, 0.21-0.89; P=0.02). An ERβ gene expression profile was identified and was markedly different from the ERα signature.
Conclusion: Expression of ERβ is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERα-negative breast cancer patients, and involves a gene expression program distinct from ERα. These results may be highly clinically significant, as in the U.S. alone, approximately 10,000 women are diagnosed annually with ERα-negative/ERβ-positive breast carcinoma who may benefit from adjuvant tamoxifen.
Purpose: Endocrine therapies such as tamoxifen are commonly given to most patients with ERα- positive breast carcinoma but are not indicated for persons with ERα-negative cancer . The factors responsible for response to tamoxifen in 5-10% of patients with ERα-negative tumors are not clear. The aim of the present study was to elucidate the biology and role of the second ER, ERβ, in endocrine therapy response.
Experimental Design: We investigated ERβ by immunohistochemistry in 353 stage II primary breast tumors from patients treated with two years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.
Results: ERβ was associated with increased survival (distant disease-free survival, P=0.01; overall survival, P=0.22), and in particular within ERα-negative patients (P=0.003; P=0.04), but not in the ERα-positive subgroup (P=0.49; P=0.88). Lack of ERβ conferred early relapse (HR, 14; 95% CI, 1.8- 106; P=0.01) within the ERα-negative subgroup even after adjustment for other markers. ERα was a independent marker only within the ERβ-negative tumors (HR, 0.44; 95% CI, 0.21-0.89; P=0.02). An ERβ gene expression profile was identified and was markedly different from the ERα signature.
Conclusion: Expression of ERβ is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERα-negative breast cancer patients, and involves a gene expression program distinct from ERα. These results may be highly clinically significant, as in the U.S. alone, approximately 10,000 women are diagnosed annually with ERα-negative/ERβ-positive breast carcinoma who may benefit from adjuvant tamoxifen.
LU TP 05-29