scholarly journals Gene Expression Profiles of Estrogen Receptor–Positive and Estrogen Receptor–Negative Breast Cancers Are Detectable in Histologically Normal Breast Epithelium

2010 ◽  
Vol 17 (2) ◽  
pp. 236-246 ◽  
Author(s):  
Kelly Graham ◽  
Xijin Ge ◽  
Antonio de las Morenas ◽  
Anusri Tripathi ◽  
Carol L. Rosenberg
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Normal Breast ◽  
Breast Cancers ◽  
Breast Epithelium ◽  
Normal Breast Epithelium ◽  
Estrogen Receptor Positive ◽  
Estrogen Receptor Negative

scholarly journals In Silico Discovery of Mitosis Regulation Networks Associated with Early Distant Metastases in Estrogen Receptor Positive Breast Cancers

2013 ◽  
Vol 12 ◽  
pp. CIN.S10329 ◽  
Author(s):  
Yuriy Gusev ◽  
Rebecca B. Riggins ◽  
Krithika Bhuvaneshwar ◽  
Robinder Gauba ◽  
Laura Sheahan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
In Silico ◽  
Expression Profiles ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Mitotic Checkpoint ◽  
Breast Cancers ◽  
Estrogen Receptor Positive

The aim of this study was to perform comparative analysis of multiple public datasets of gene expression in order to identify common genes as potential prognostic biomarkers. Additionally, the study sought to identify biological processes and pathways that are most significantly associated with early distant metastases (<5 years) in women with estrogen receptor-positive (ER+) breast tumors. Datasets from three published studies were selected for in silico analysis of gene expression profiles of ER+ breast cancer, using time to distant metastasis as the clinical endpoint. A subset of 44 differently expressed genes (DEGs) was found common to all three studies and characterized by mitotic checkpoint genes and pathways that regulate mitotic spindle and chromosome dynamics. DEG promoter regions were enriched with NFY binding sites. Analysis of miRNA target sites identified significant enrichment of miR-192, miR-193B, and miR-16–1 targets. Aberrant mitotic regulation could drive increased genomic instability leading to a progression towards an early onset metastatic phenotype. The relative importance of mitotic instability may reflect the clinical utility of mitotic poisons in metastatic breast cancer, including poisons such as the taxanes, epothilones, and vinca alkaloids.

scholarly journals Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance

2015 ◽  
Vol 8 ◽  
pp. CPath.S31563 ◽  
Author(s):  
Jaafar Makki
Keyword(s):  
Gene Expression ◽  
Breast Carcinoma ◽  
Clinical Course ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Classification ◽  
Developed Countries ◽  
Breast Cancers ◽  
Wide Scope ◽  
Histological Subtypes

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of ≥1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.

scholarly journals Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

2017 ◽  
Vol 35 (24) ◽  
pp. 2814-2819 ◽  
Author(s):  
Anne Kuijer ◽  
Marieke Straver ◽  
Bianca den Dekker ◽  
Annelotte C.M. van Bommel ◽  
Sjoerd G. Elias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Early Stage Breast Cancer ◽  
Er Positive ◽  
Test Result

Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. Results Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. Conclusion In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.

scholarly journals Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients

2007 ◽  
Vol 122 (7) ◽  
pp. 1557-1566 ◽  
Author(s):  
Anusri Tripathi ◽  
Chialin King ◽  
Antonio de la Morenas ◽  
Victoria Kristina Perry ◽  
Bohdana Burke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Breast Epithelium ◽  
Normal Breast Epithelium

scholarly journals A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peiling Xie ◽  
Rui An ◽  
Shibo Yu ◽  
Jianjun He ◽  
Huimin Zhang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Outcomes ◽  
Immune Escape ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Characteristics ◽  
Consensus Clustering ◽  
Breast Cancers ◽  
Her2 Breast Cancer

Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.

scholarly journals Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol

2004 ◽  
Vol 33 (1) ◽  
pp. 243-252 ◽  
Author(s):  
H Watanabe ◽  
A Suzuki ◽  
M Goto ◽  
DB Lubahn ◽  
H Handa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Estrogenic Activity ◽  
Expression Profiles ◽  
Endocrine System ◽  
Gene Expression Profiles ◽  
Binding Activity ◽  
High Dose ◽  
Tissue Specific ◽  
Liver Gene

Alkylphenols perturb the endocrine system and are considered to have weak estrogenic activities. Although it is known that nonylphenol can bind weakly to the estrogen receptor, it is unclear whether all reported effects of nonylphenol are attributable to its estrogen receptor-binding activity. In order to examine whether alkylphenols have similar effects to the natural hormone, estradiol, we used a mouse model to examine the effects of nonylphenol on gene expression and compared it with estradiol. DNA microarray analysis revealed that, in the uterus, most of the genes activated by this alkylphenol at a high dose (50 mg/kg) were also activated by estradiol. At lower doses, nonylphenol (0.5 mg/kg and 5 mg/kg) had little effect on the genes that were activated by estradiol. Thus, we concluded that the effects of nonylphenol at a high dose (50 mg/kg) were very similar to estradiol in uterine tissue. Moreover, since evaluation of estrogenic activity by gene expression levels was comparable with the uterotrophic assay, it indicated that analysis of gene expression profiles can predict the estrogenic activities of chemicals. In contrast to the similar effects of nonylphenol and estradiol observed in the uterus, in the liver, gene expression was more markedly affected by nonylphenol than by estradiol. This indicated that, in the liver, nonylphenol could activate another set of genes that are distinct from estrogen-responsive genes. These results indicated that nonylphenol has very similar effects to estradiol on gene expression in uterine but not in liver tissue, indicating that tissue-specific effects should be considered in order to elucidate the distinct effects of alkylphenols.

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