Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140143 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side-effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for Phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for three months. Blood and breast tissue samples were collected at baseline and post-treatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood, DNA methylation and cytology in random periareolar fine needle aspirates, and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and RT-PCR) in the tissue core samples. Tamoxifen downregulated ets-oncogene family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1 or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen also modulated expression of RAB GTPases, and several genes involved in epithelial-stromal interaction, and reduced tumor suppressor gene methylation. Three months of tamoxifen did not affect breast tissue composition, cytological atypia, preneoplasia or apoptosis. Tamoxifen may durably reduce breast cancer risk through downregulation of ETV4 and ETV5 which could deplete mammary progenitor populations. This pathway has the potential to provide novel targets and early response biomarkers for phase II prevention trials. Randomized prospective double blinded placebo-controlled trial of tamoxifen (20 mg daily) versus placeo in women at increased risk for breast cancer. Gene expression was assessed in whole breast tissue cores obtained at baseline and after three months of treatment for 35 women. Core biopsies were obtained in the late luteal phase (day 28 +/- 2) for premenopausal women (N = 19). Breast lobules from the baseline and post-treatment cores were microdissected for 5 tamoxifen subjects.
2011-07-21 | E-GEOD-29338 | biostudies-arrayexpress
Project description:Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side-effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for Phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for three months. Blood and breast tissue samples were collected at baseline and post-treatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood, DNA methylation and cytology in random periareolar fine needle aspirates, and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and RT-PCR) in the tissue core samples. Tamoxifen downregulated ets-oncogene family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1 or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen also modulated expression of RAB GTPases, and several genes involved in epithelial-stromal interaction, and reduced tumor suppressor gene methylation. Three months of tamoxifen did not affect breast tissue composition, cytological atypia, preneoplasia or apoptosis. Tamoxifen may durably reduce breast cancer risk through downregulation of ETV4 and ETV5 which could deplete mammary progenitor populations. This pathway has the potential to provide novel targets and early response biomarkers for phase II prevention trials.
2011-07-22 | GSE29338 | GEO
Project description:Estrogen receptor (ER)-positive breast cancer (BC) patients face constant threat of distant recurrence up to 20 years of diagnosis, reaching a total of 30% recurrence and a mortality rate of more than 25%. Here, we examined the influence of long-term tamoxifen treatment in metastatic niche formation in vivo. To test this, placebo or tamoxifen pellets were inoculateded in the 8-week old MMTV-PyMT mouse model and analyses were conducted 5-weeks after the treatment. Despite a reduction in primary tumor size compared to the placebo-treated group, lung metastasis was increased in the tamoxifen-treated mouse. At this point, scRNA-seq was also performed in mouse lungs of either placebo or tamoxifen-treated MMTV-PyMT mouse lungs, which revealed an increase in an interstitial macrophage subpopulation in the tamoxifen-treated group. This Prg4+ macrophages had enhanced lipid metabolic gene signatures and strongly interacted with fibroblasts via TGFβ1 signaling pathway, potentially contributing to lung fibrosis. This study identifies long-term tamoxifen treatment as a risk factor for promoting breast cancer cell resistance and altering the lung microenvironment, thereby facilitating lung metastasis.
2025-08-28 | GSE304859 | GEO
Project description:Breast cancer is one of the most commonly diagnosed cancers among women and the leading cause of death in women under 50. The majority of breast cancers are estrogen receptor α-positive (ER+) and are most commonly treated with hormonal therapy that inhibits ER activity, such as tamoxifen. The TP53 tumor suppressor gene, encoding the p53 protein, is the most frequently mutated gene in breast cancer, and TP53 mutations are associated with diminished tamoxifen response and worse prognosis for breast cancer patients. Here, we report that in breast cancer cells p53 and ER cooperate to regulate the expression of a set of genes encoding chromatin modifiers. The net result is a global increase in H3K4me3 and decrease in H3K9me3 chromatin marks. The resultant “open” chromatin is associated with increased transcription of luminal cell identity genes and enhanced tamoxifen sensitivity. Conversely, diminished p53 control of these chromatin modulators is associated with the evolution of tamoxifen resistance and cancer stem cell properties.
2025-10-14 | PXD065898 | Pride
Project description:Adjuvant tamoxifen is a valid treatment option for women with estrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence. Patients were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005.
2014-07-01 | GSE46823 | GEO
Project description:Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer. In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT. Keywords: Gene expression profiling analysis Formalin fixed paraffin embedded tumor blocks with enough tumor tissue for RNA extraction were available from 108 cases (69 from placebo arm and 39 from tamoxifen arm) of the 264 that experienced invasive breast cancer (175 in placebo arm and 89 in tamoxifen arm) in BCPT before unblindings . Central ER immunohistochemistry identified 84 of them as ER positive (57 from placebo arm and 27 from tamoxifen arm). A novel protocol was developed and used to obtain microarray gene expression profiling from the degraded or fragmented RNA extracted from formalin fixed paraffin blocks.Hybridization intensity data were compiled using Partek Genomic Suite. After quantile normalization, genes with mean intensity below 500 were filtred out, which left 7743 probes with informative data. Data were log2 transformed for statistical analysis.
2011-12-08 | E-GEOD-12665 | biostudies-arrayexpress
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Breast cancer is one of the most commonly diagnosed cancers among women and the leading cause of death in women under 50. The majority of breast cancers are estrogen receptor α-positive (ER+). Historically, these cancers are treated with therapies, such as tamoxifen, that inhibit ER activity. The TP53 tumor suppressor gene, encoding the p53 protein, is the most frequently mutated gene in breast cancer, and TP53 mutations are associated with diminished tamoxifen response and worse prognosis. Here, we report that in breast cancer cells p53 and ER cooperate to regulate the expression of a set of genes encoding chromatin modifiers. The net result is a global increase in H3K4me3 and decrease in H3K9me3 chromatin marks. The resultant “open” chromatin is associated with increased transcription of luminal cell identity genes and augmented tamoxifen sensitivity. Conversely, diminished p53 control of these chromatin modulators is associated with the evolution of tamoxifen resistance and cancer stem cell properties.
2025-11-13 | GSE292361 | GEO
Project description:Breast cancer is one of the most commonly diagnosed cancers among women and the leading cause of death in women under 50. The majority of breast cancers are estrogen receptor α-positive (ER+). Historically, these cancers are treated with therapies, such as tamoxifen, that inhibit ER activity. The TP53 tumor suppressor gene, encoding the p53 protein, is the most frequently mutated gene in breast cancer, and TP53 mutations are associated with diminished tamoxifen response and worse prognosis. Here, we report that in breast cancer cells p53 and ER cooperate to regulate the expression of a set of genes encoding chromatin modifiers. The net result is a global increase in H3K4me3 and decrease in H3K9me3 chromatin marks. The resultant “open” chromatin is associated with increased transcription of luminal cell identity genes and augmented tamoxifen sensitivity. Conversely, diminished p53 control of these chromatin modulators is associated with the evolution of tamoxifen resistance and cancer stem cell properties.
2025-11-13 | GSE292362 | GEO