scholarly journals Estrogen Receptor (ESR1) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer

2011 ◽  
Vol 29 (31) ◽  
pp. 4160-4167 ◽  
Author(s):  
Chungyeul Kim ◽  
Gong Tang ◽  
Katherine L. Pogue-Geile ◽  
Joseph P. Costantino ◽  
Frederick L. Baehner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Tamoxifen Resistance ◽  
Linear Predictor ◽  
Treatment And Prevention ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.

scholarly journals Relationship Between Plasma Estradiol Levels and Estrogen-Responsive Gene Expression in Estrogen Receptor–Positive Breast Cancer in Postmenopausal Women

2010 ◽  
Vol 28 (7) ◽  
pp. 1161-1167 ◽  
Author(s):  
Anita K. Dunbier ◽  
Helen Anderson ◽  
Zara Ghazoui ◽  
Elizabeth J. Folkerd ◽  
Roger A'Hern ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Multivariable Analysis ◽  
Independent Set ◽  
Breast Cancers ◽  
Plasma Estradiol ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose To determine whether plasma estradiol (E2) levels are related to gene expression in estrogen receptor (ER)–positive breast cancers in postmenopausal women. Materials and Methods Genome-wide RNA profiles were obtained from pretreatment core-cut tumor biopsies from 104 postmenopausal patients with primary ER-positive breast cancer treated with neoadjuvant anastrozole. Pretreatment plasma E2 levels were determined by highly sensitive radioimmunoassay. Genes were identified for which expression was correlated with pretreatment plasma E2 levels. Validation was performed in an independent set of 73 ER-positive breast cancers. Results The expression of many known estrogen-responsive genes and gene sets was highly significantly associated with plasma E2 levels (eg, TFF1/pS2, GREB1, PDZK1 and PGR; P < .005). Plasma E2 explained 27% of the average expression of these four average estrogen-responsive genes (ie, AvERG; r = 0.51; P < .0001), and a standardized mean of plasma E2 levels and ER transcript levels explained 37% (r, 0.61). These observations were validated in an independent set of 73 ER-positive tumors. Exploratory analysis suggested that addition of the nuclear coregulators in a multivariable analysis with ER and E2 levels might additionally improve the relationship with the AvERG. Plasma E2 and the standardized mean of E2 and ER were both significantly correlated with 2-week Ki67, a surrogate marker of clinical outcome (r = −0.179; P = .05; and r = −0.389; P = .0005, respectively). Conclusion Plasma E2 levels are significantly associated with gene expression of ER-positive breast cancers and should be considered in future genomic studies of ER-positive breast cancer. The AvERG is a new experimental tool for the study of putative estrogenic stimuli of breast cancer.

scholarly journals Concordance between Immunohistochemistry and Microarray Gene Expression Profiling for Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Statuses in Breast Cancer Patients in Lebanon

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ghina B. Fakhri ◽  
Reem S. Akel ◽  
Maya K. Khalil ◽  
Deborah A. Mukherji ◽  
Fouad I. Boulos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Concordance Rate ◽  
Kappa Score ◽  
Microarray Gene Expression ◽  
Microarray Gene

Introduction. Accurate evaluation of estrogen and progesterone receptors and HER2 is critical when diagnosing invasive breast cancer for optimal treatment. The current evaluation method is via immunohistochemistry (IHC). In this paper, we compared results of ER, PR, and HER2 from microarray gene expression to IHC in 81 fresh breast cancer specimens. Methods. Gene expression profiling was performed using the GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix Inc). Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 status was performed using standard methods at a CAP-accredited pathology laboratory. Concordance rates, agreement measures, and kappa scores were calculated for both methods. Results. For ER, Kappa score was 0.918 (95% CI, 0.77.3–1.000) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). For PR, Kappa score was 0.652 (95% CI, 0.405–0.849) and concordance rate was 86.4% (95% CI, 77%–93%). For HER2, Kappa score was 0.709 (95% CI, 0.428–0.916) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). Conclusion. Our results are in line with the available evidence with the concordance rate being the lowest for the progesterone receptor. In general, microarray gene expression and IHC proved to have high concordance rates. Several factors can increase the discordance rate such as differences in sample processing.

scholarly journals Gene Expression Profiling Reveals New Aspects of PIK3CA Mutation in ERalpha-Positive Breast Cancer: Major Implication of the Wnt Signaling Pathway

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15647 ◽  
Author(s):  
Magdalena Cizkova ◽  
Géraldine Cizeron-Clairac ◽  
Sophie Vacher ◽  
Aurélie Susini ◽  
Catherine Andrieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Wnt Signaling ◽  
Gene Expression Profiling ◽  
Signaling Pathway ◽  
Expression Profiling ◽  
Pik3ca Mutation ◽  
Wnt Signaling Pathway ◽  
Major Implication ◽  
Positive Breast Cancer

scholarly journals Network-based Approach to Identify Prognosis-related Genes in Tamoxifen-treated Patients With Estrogen Receptor-positive Breast Cancer

2020 ◽  
Author(s):  
Yanyan Wang ◽  
Xiaonan Gong ◽  
Yujie Zhang
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Targeting ◽  
Quantitative Polymerase Chain Reaction ◽  
Tamoxifen Resistance ◽  
The Cancer Genome Atlas ◽  
Tamoxifen Treatment ◽  
Hub Genes ◽  
Er Positive ◽  
Positive Breast Cancer

Abstract Background: The estrogen receptor (ER) antagonist tamoxifen is the most commonly used endocrine therapy for ER-positive breast cancer. However, tamoxifen resistance remains a major cause of cancer recurrence and progression. Here, we aimed to identify hub genes involved in the progression and prognosis of ER-positive breast cancer following tamoxifen treatment.Results: Microarray data (GSE9838) for 155 tamoxifen-treated primary ER-positive breast cancer samples were obtained from the Gene Expression Omnibus database. In total, 1706 differentially expressed genes (DEGs) associated with tamoxifen resistance, including 859 upregulated genes and 847 downregulated genes, were identified. These DEGs were mainly enriched in functions such as protein targeting to the ER and pathways such as ribosome and oxidative phosphorylation.Weighted correlation network analysis (WGCNA) clustered genes into 13 modules, among which the tan and blue modules were the most significantly related to prognosis. From these two modules, we further identified three prognosis-related hub genes (GRSF1, MAPT, and REC8) via survival analysis. High expression ofGRSF1 predicted poor prognosis, whereas MAPT andREC8indicated favorable survival outcomes in all patients with breast cancer and in patients with ER-positive breast cancer based on The Cancer Genome Atlas database. These hub genes were further verified by reverse transcription quantitative polymerase chain reaction.Conclusion: Our findings established novel prognostic biomarkers to predict tamoxifen sensitivity, which may facilitate individualized management of breast cancer.

scholarly journals Gene Expression Profiling in Estorogen Receptor Positive Breast Cancer With Cancer Stem-Like Cells

2012 ◽  
Vol 23 ◽  
pp. ix87
Author(s):  
Y. Tsunoda ◽  
M. Sakamoto ◽  
E. Fukma ◽  
T. Sawada ◽  
A. Sasaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Positive Breast Cancer
Sign in / Sign up

Export Citation Format

Share Document