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- Gruvberger, Sofia, et al.
(författare)
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Estrogen receptor beta expression is associated with tamoxifen response in ER alpha-negative breast carcinoma
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:7, s. 1987-1994
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Tidskriftsartikel (refereegranskat)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 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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| 2. |
- Gruvberger, Sofia, et al.
(författare)
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Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns
- 2001
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Ingår i: Cancer Research. - 1538-7445. ; 61:16, s. 5979-5984
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the phenotype associated with estrogen receptor alpha (ER) expression in breast carcinoma, gene expression profiles of 58 node-negative breast carcinomas discordant for ER status were determined using DNA microarray technology. Using artificial neural networks as well as standard hierarchical clustering techniques, the tumors could be classified according to ER status, and a list of genes which discriminate tumors according to ER status was generated. The artificial neural networks could accurately predict ER status even when excluding top discriminator genes, including ER itself. By reference to the serial analysis of gene expression database, we found that only a small proportion of the 100 most important ER discriminator genes were also regulated by estradiol in MCF-7 cells. The results provide evidence that ER+ and ER- tumors display remarkably different gene-expression phenotypes not solely explained by differences in estrogen responsiveness.
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| 3. |
- Gruvberger, Sofia, et al.
(författare)
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Expression profiling to predict outcome in breast cancer: the influence of sample selection
- 2003
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 5:1, s. 23-26
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Tidskriftsartikel (refereegranskat)abstract
- Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor- status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor--positive and estrogen receptor--negative tumors.
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| 4. |
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| 5. |
- Saal, Lao, et al.
(författare)
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Bioarray software environment: a platform for comprehensive management and analysis of microarray data
- 2002
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906. ; 3:8, s. 1-2002
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Tidskriftsartikel (refereegranskat)abstract
- The microarray technique requires the organization and analysis of vast amounts of data. These data include information about the samples hybridized, the hybridization images and their extracted data matrices, and information about the physical array, the features and reporter molecules. We present a web-based customizable bioinformatics solution called BioArray Software Environment (BASE) for the management and analysis of all areas of microarray experimentation. All software necessary to run a local server is available for free and the source code may be downloaded from http://base.thep.lu.se.
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