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Estrogen receptor beta expression is associated with tamoxifen response in ER alpha-negative breast carcinoma

Gruvberger, Sofia LU ; Bendahl, Pär-Ola LU ; Saal, Lao H LU ; Laakso, Mervi; Hegardt, Cecilia LU ; Edén, Patrik LU ; Peterson, Carsten LU ; Malmström, Per LU ; Isola, Jorma LU and Borg, Åke LU , et al. (2007) In Clinical Cancer Research 13(7). p.1987-1994
Abstract

PURPOSE: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERalpha)-positive breast carcinoma but are not indicated for persons with ERalpha-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERalpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERbeta, in patients treated with adjuvant tamoxifen.

EXPERIMENTAL DESIGN: We investigated ERbeta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.

RESULTS: ERbeta... (More)

PURPOSE: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERalpha)-positive breast carcinoma but are not indicated for persons with ERalpha-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERalpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERbeta, in patients treated with adjuvant tamoxifen.

EXPERIMENTAL DESIGN: We investigated ERbeta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.

RESULTS: ERbeta was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERalpha-negative patients (P = 0.003; P = 0.04), but not in the ERalpha-positive subgroup (P = 0.49; P = 0.88). Lack of ERbeta conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERalpha-negative subgroup even after adjustment for other markers. ERalpha was an independent marker only within the ERbeta-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERbeta gene expression profile was identified and was markedly different from the ERalpha signature.

CONCLUSION: Expression of ERbeta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERalpha-negative breast cancer patients and involves a gene expression program distinct from ERalpha. These results may be highly clinically significant, because in the United States alone, approximately 10,000 women are diagnosed annually with ERalpha-negative/ERbeta-positive breast carcinoma and may benefit from adjuvant tamoxifen.

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Biomarkers, Tumor, Breast Neoplasms, Chemotherapy, Adjuvant, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Gene Expression, Gene Expression Profiling, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Oligonucleotide Array Sequence Analysis, Prognosis, Randomized Controlled Trials as Topic, Selective Estrogen Receptor Modulators, Tamoxifen, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
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Clinical Cancer Research
volume
13
issue
7
pages
8 pages
publisher
American Association for Cancer Research
external identifiers
  • wos:000245660800007
  • scopus:34247491944
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-06-1823
project
CREATE Health
language
English
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yes
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c7cb4587-604c-4f6d-8ddd-42c9023f06cc (old id 669460)
date added to LUP
2007-12-11 11:03:46
date last changed
2017-09-03 03:48:27
@article{c7cb4587-604c-4f6d-8ddd-42c9023f06cc,
  abstract     = {<p>PURPOSE: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERalpha)-positive breast carcinoma but are not indicated for persons with ERalpha-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERalpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERbeta, in patients treated with adjuvant tamoxifen.</p><p>EXPERIMENTAL DESIGN: We investigated ERbeta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.</p><p>RESULTS: ERbeta was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERalpha-negative patients (P = 0.003; P = 0.04), but not in the ERalpha-positive subgroup (P = 0.49; P = 0.88). Lack of ERbeta conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERalpha-negative subgroup even after adjustment for other markers. ERalpha was an independent marker only within the ERbeta-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERbeta gene expression profile was identified and was markedly different from the ERalpha signature.</p><p>CONCLUSION: Expression of ERbeta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERalpha-negative breast cancer patients and involves a gene expression program distinct from ERalpha. These results may be highly clinically significant, because in the United States alone, approximately 10,000 women are diagnosed annually with ERalpha-negative/ERbeta-positive breast carcinoma and may benefit from adjuvant tamoxifen.</p>},
  author       = {Gruvberger, Sofia and Bendahl, Pär-Ola and Saal, Lao H and Laakso, Mervi and Hegardt, Cecilia and Edén, Patrik and Peterson, Carsten and Malmström, Per and Isola, Jorma and Borg, Åke and Fernö, Mårten},
  issn         = {1078-0432},
  keyword      = {Biomarkers, Tumor,Breast Neoplasms,Chemotherapy, Adjuvant,Estrogen Receptor alpha,Estrogen Receptor beta,Female,Gene Expression,Gene Expression Profiling,Humans,Immunohistochemistry,Kaplan-Meier Estimate,Oligonucleotide Array Sequence Analysis,Prognosis,Randomized Controlled Trials as Topic,Selective Estrogen Receptor Modulators,Tamoxifen,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {7},
  pages        = {1987--1994},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Estrogen receptor beta expression is associated with tamoxifen response in ER alpha-negative breast carcinoma},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-06-1823},
  volume       = {13},
  year         = {2007},
}