TransCONFIRM gene expression analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76040 | GEO | 2015/12/16
SECONDARY ACCESSION(S): PRJNA306048
REPOSITORIES: GEO
Similar Datasets
Project description:gene expression analysis ussing microarray analysis of a subset of primary tumors collected from patients that participated in the CONFIRM phase III study, which randomized post menopausal patients with ER+ metastatic breast cancer to fulvestrant 500mg and fulvestrant 250mg. Primary tumor samples were collected from patients participating in the CONFIRM study.
2015-12-16 | E-GEOD-76040 | biostudies-arrayexpress
Project description:The NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumours) trial compared the clinical and biological activity of fulvestrant 500 mg vs 250 mg in the neoadjuvant setting. In this multi-centre phase II study, post-menopausal women with operable, locally advanced (T2, 3, 4b; N0-3; M0) ER-positive breast tumours were randomised to receive neoadjuvant treatment with either dose of fulvestrant for 16 weeks before surgery. Tumour core biopsies were obtained at baseline, 4 weeks and at surgery for assessment of changes in biomarker expression. Tumour volumes were measured by 3-D ultrasound at the same timepoints. In this trial, the percentage of patients who showed a reduction in tumour volume or stabilisation of disease (using RECIST criteria) after treatment with fulvestrant 500 mg was 36% (26 out of 69 patients). Therefore, within a population of endocrine-therapy naive patients whose tumours were confirmed as being ER-positive at the time of study entry, there is a subgroup who gained particular clinical benefit from fulvestrant treatment. These clinical response data together with the availability of biological response information and frozen tumour tissue from participants makes the NEWEST trial an attractive setting in which to investigate the potential of new markers of response to fulvestrant. 42 samples
2014-01-08 | E-GEOD-48905 | biostudies-arrayexpress
Project description:Purpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined. Experimental Design: We investigated the specific role of increased CDK6 expression in fulvestrant-resistant cells by gene knockdown and treatment with palbociclib, and evaluated the effect in cell proliferation, apoptosis and kinase activity. Furthermore, we evaluated CDK6 expression in metastatic samples from breast cancer patients treated or not with fulvestrant. Results: We found increased expression of CDK6 in two fulvestrant-resistant cell models vs. sensitive cells. Reduction of CDK6 expression impaired fulvestrant-resistant cell growth and induced apoptosis by reducing p70 ribosomal S6 kinase 2 activity. Treatment with palbociclib re-sensitized fulvestrant-resistant cells to fulvestrant through alteration of retinoblastoma phosphorylation. High CDK6 levels in metastatic samples from breast cancer patients treated with fulvestrant (N=45) correlated significantly with shorter progression-free survival (PFS) (p=0.0006), while no association was observed in patients receiving other endocrine treatments (N=41, p=0.874). Conclusions: Our results indicate that upregulation of CDK6 may be an important mechanism in overcoming fulvestrant-mediated growth inhibition in breast cancer cells. Patients with advanced ER+ breast cancer exhibiting high CDK6 expression in the metastatic lesions show shorter PFS upon fulvestrant treatment and thus may benefit from the addition of CDK4/6 inhibitors in their therapeutic regimens.
2017-02-08 | GSE74391 | GEO
Project description:The NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumours) trial compared the clinical and biological activity of fulvestrant 500 mg vs 250 mg in the neoadjuvant setting. In this multi-centre phase II study, post-menopausal women with operable, locally advanced (T2, 3, 4b; N0-3; M0) ER-positive breast tumours were randomised to receive neoadjuvant treatment with either dose of fulvestrant for 16 weeks before surgery. Tumour core biopsies were obtained at baseline, 4 weeks and at surgery for assessment of changes in biomarker expression. Tumour volumes were measured by 3-D ultrasound at the same timepoints. In this trial, the percentage of patients who showed a reduction in tumour volume or stabilisation of disease (using RECIST criteria) after treatment with fulvestrant 500 mg was 36% (26 out of 69 patients). Therefore, within a population of endocrine-therapy naive patients whose tumours were confirmed as being ER-positive at the time of study entry, there is a subgroup who gained particular clinical benefit from fulvestrant treatment. These clinical response data together with the availability of biological response information and frozen tumour tissue from participants makes the NEWEST trial an attractive setting in which to investigate the potential of new markers of response to fulvestrant.
2014-01-08 | GSE48905 | GEO
Project description:Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. Examination of treatment-naïve primary tumors in five patients revealed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. These mutations were mutually exclusive with ER mutations, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that these mutations conferred estrogen independence. In addition, and in contrast to ER mutations, these mutations resulted in resistance to tamoxifen, fulvestrant, and the CDK4/6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib, highlighting an effective treatment strategy in these patients.
2018-10-19 | GSE121411 | GEO
Project description:To gain insight into the gene expression profile of breast patient derived organoids (PDOs) under endocrine therapy, and how cancer associated fibroblasts (CAFs) might influence gene expression and stimulate resistance, we performed RNA sequencing on three of the metastatic PDOs treated with control media and CAF-conditioned media, in the presence and absence of Fulvestrant (4-day treatment). These data revealed that Fulvestrant significantly suppressed the ER signature in the PDOs, suggesting that the ER-pathway is still active in these tumors although the patients had relapsed on ER-targeting agents (Tamoxifen, Letrozole).
2023-06-27 | GSE216540 | GEO
Project description:The PI3Kalpha-specific inhibitor Alpelisib (BYL719) has been approved for the treatment of metastatic ER+/HER2- breast cancer patients in combination with Fulvestrant. After initial response, patients develop drug resistance and disease relapses. In order to identify signalling pathways contributing to the acquired resistance to BYL719 in breast cancer, we generated BYL719-resistant T47D cells and used them together with the parental cells to perform label-free quantitative phosphoproteomics.
2023-12-05 | PXD033956 | Pride
Project description:Oestrogen receptor alpha (ER, gene symbol ESR1) is the most important prognostic and treatment-predictive biomarker in breast cancer. Drugs targeting oestrogen and the ER for endocrine therapy of breast cancer include aromatase inhibitors, the selective ER modulator tamoxifen and the selective ER degrader fulvestrant. Tumours can develop resistance to endocrine therapy through several mechanisms, which is often linked to altered expression of the ER. To investigate the role of promoter methylation in regulation of ER expression, we used bisulfite sequencing to measure methylation at CpG sites in alternative ER promoter regions for six cell line models of fulvestrant resistance. Both CpG methylation and expression of alternative first exons changed dynamically with striking differences between cell lines that had stable or unstable resistance upon fulvestrant withdrawal. Methylation at some CpG sites was strongly negatively correlated with expression of specific first exons. In a breast tumour cohort, higher relative expression of upstream alternative first exons was associated with worse prognosis in post-menopausal women with ER-positive tumours who received endocrine therapy.
2024-08-06 | GSE251791 | GEO
Project description:Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
2011-12-20 | GSE33658 | GEO
Project description:Most ER+ breast cancers (BC) express androgen receptors (AR). This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) was performed to determine if the addition of AR blockade to Fulv would increase the percentage of patients with limited residual tumor at time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Stratification factors were clinical node and T-stage. Fresh tumor biopsies were required at study entry, after 4 weeks on therapy (W5), and at surgery (week 17).
2024-06-30 | GSE271080 | GEO