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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The NEWEST trial

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas Jensen

PROVIDER: E-GEOD-48905 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The NEWEST trial

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:The goal of the study was to identify a gene expression signature capable of predicting a pathological complete response following neoadjuvant anthracycline-based chemotherapy of breast cancer. The samples were taken from the FEC arm (5-fluorouracil, epirubicin, cyclophosphamide) of the EORTC 10994 trial. EORTC 10994 is a phase III clinical trial comparing FEC with ET (epirubicin, docetaxel) in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 200 ng total RNA per chip was amplified using the Affymetrix small sample protocol (IVT then Enzo). 102 tumours were tested on Affymetrix X3P chips. Single biopsies were tested per tumour. The CEL files were quantile normalised using rma. The clinical response measure was pathological complete response (pCR, disappearance of the tumour after chemotherapy with at most scattered invasive cells detected by histology). 102 tumors

2008-12-19 | E-GEOD-4779 | biostudies-arrayexpress

Pre-treatment expression data from neoadjuvant platinum & bevacizumab treated triple negative breast cancer patients

Project description:Gene expression data from 21 triple negative breast cancer samples treated with cisplatin & bevacizumab in the neoadjuvant setting as part of a clinical trial. Gene expression data RMA normalized was used to find predictors of platinum sensitivity

2018-02-19 | GSE103668 | GEO

2008-12-19 | GSE4779 | GEO

A phase II neoadjuvant trial of anastrozole (A), fulvestrant (F) and gefitinib (I - iressa) in patients with newly diagnosed estrogen receptor positive breast cancer

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

Predicting Response and Survival in Chemotherapy-Treated Triple-Negative Breast Cancer

Project description:Gene expression data of pre-treatment samples of GEICAM2006-03 TNBC trial Patients were randomized to carboplatin or no carboplatin in the neoadjuvant setting

2014-08-11 | GSE58479 | GEO

Synergistic targeting of estrogen-receptor positive breast cancers by MDM2 inhibition in combination with endocrine therapy or CDK4/6 inhibition

Project description:Here we characterise the response of models of ER-positive breast cancer to treatment with the small molecule MDM2 inhibitor NVP-CGM097, a dihydroisoquinolinone derivative currently evaluated in a phase I clinical trial. We show that NVP-CGM097 reduces tumour cell viability of in vitro and in vivo models of endocrine sensitive, endocrine resistant and palbociclib (CDK4/6 inhibitor) resistant p53 wildtype (p53wt) ER-positive breast cancer. NVP-CGM097 synergises with both fulvestrant and palbociclib in models of therapy resistance. Importantly, we identify the key mechanisms of the synergistic interactions between NVP-CGM097 and endocrine therapy, which occurs through the inhibition of E2F Targets and G2M Checkpoint signalling and induction of senescence, rather than depending upon upregulation of p53 dependent apoptotic pathways. Moreover, we find these same pathways are synergistically targeted during the combination treatment of ER positive breast cancer models with NVP-CGM097 and palbociclib. This indicates the genuine potential of MDM2 inhibition as therapy in advanced ER-positive breast cancer as combination endocrine therapy and CDK4/6 inhibitor treatment becomes embedded as standard of care.

2020-04-01 | GSE140758 | GEO

Illumina Infinium HumanMethylation450 BeadChip profiling of paediatric high grade gliomas from the HERBY clinical trial

Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas within the HERBY clinical trial. The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem HGG between the ages of 3-18yrs. The 450K methylation array was used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations.

2018-05-11 | E-MTAB-5552 | biostudies-arrayexpress

Transcription profiling of human tumours at baseline and after 21 days of treatment with sorafenib and dacarbazine

Project description:Background New approaches are needed to improve prognostic accuracy for treatment response and to explore the complexities of drug effects on human tumours. We developed a strategy of global genomic investigation of sequential tumor biopsies at baseline and 21 days post-treatment, and applied this approach in a phase I study of sorafenib plus dacarbazine in patients with solid tumours. Methods 23 patients received 21-day cycles of oral sorafenib, 400 mg twice daily and dacarbazine, 1000 mg/m2 by 1-h intravenous infusion on day 1. Efficacy was assessed using response evaluation criteria in solid tumours. Differential gene expression was assessed through genomic microarray analysis of biopsy tissue from the same tumour at baseline and on day 21. Seven parameters characterizing vascularisation using dynamic enhanced-contrast ultrasonography (DCE-US) were assessed. Changes from baseline in the two parameters were characterized for patients with and without a clinical response to treatment at 3 months.Findings 23 patients were evaluable for efficacy and 17 for gene expression and DCE-US analyses. One patient had a partial response; 14 had stable disease. Genomic analyses identified a 247-gene signature that distinguished progressors from nonprogressors at 3 months. Expression of four genes was significantly associated with progression at 3 months. Functional parameters of DCE-US representing blood volume at baseline, day 8, and day 21 correlated with 3-month disease progression status.Interpretation This novel approach of sequential investigations in a phase I trial was feasible, detecting early changes in gene expression and tumour vascularity that may be predictive of clinical outcome.

2010-07-31 | E-TABM-760 | biostudies-arrayexpress

Proteome characterization of the neoadjuvant clinical trial PROMIX

Project description:Proteome characterization of the neoadjuvant clinical trial PROMIX. https://www.clinicaltrials.gov/ct2/show/NCT00957125 Patients received six rounds of chemotherapy with epirubicin and docetaxel, and if PR or PD after the second course, bevacizumab.

2024-03-19 | PXD039529 | JPOST Repository

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