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

Author:
  • Sofia Gruvberger
  • Pär-Ola Bendahl
  • Lao H Saal
  • Mervi Laakso
  • Cecilia Hegardt
  • Patrik Edén
  • Carsten Peterson
  • Per Malmström
  • Jorma Isola
  • Åke Borg
  • Mårten Fernö
Publishing year: 2007
Language: English
Pages: 1987-1994
Publication/Series: Clinical Cancer Research
Volume: 13
Issue: 7
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

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.

Keywords

  • Cancer and Oncology
  • 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

Other

Published
  • CREATE Health
  • Personalized Breast Cancer Treatment
  • ISSN: 1078-0432
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90