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Neoadjuvant anastrozole alone or with gefitinib in early breast cancer

ABSTRACT: Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks.

ORGANISM(S): Homo sapiens

PROVIDER: GSE48906 | GEO | 2014/01/08

SECONDARY ACCESSION(S): PRJNA212259

REPOSITORIES: GEO

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Neoadjuvant anastrozole alone or with gefitinib in early breast cancer

Project description:Trial 223 was a placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. We used patients from arm B and C: anastrozole 1mg/d for the duration of the 16 week period plus placebo 1 tablet/d orally for 2 weeks. Patients in arm B were followed by gefitinib 250mg/d orally for 14 weeks whereas patients in arm C continued with placebo for 14 weeks. 96 samples

2014-01-08 | E-GEOD-48906 | biostudies-arrayexpress

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

T47D cells; Anastrozole RNA-seq

Project description:The objective of the RNAseq is to identify genes regulated by anastrozole, and the difference in genes regulated by anastrozole and estradiol.

2020-09-08 | GSE150683 | GEO

Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial

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

T47D cells; Anastrozole RNA-seq

Project description:T47D cells; Anastrozole RNA-seq

| PRJNA633145 | ENA

ACTG A5258 Clinical administration of chloroquine to patients with untreated chronic HIV infection to reduce immune activation

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2016-07-15 | E-GEOD-71063 | biostudies-arrayexpress

ACTG A5258 Clinical administration of chloroquine to HIV-infected patients receiving antiretroviral therapy to reduce immune activation

2016-07-15 | E-GEOD-71064 | biostudies-arrayexpress

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Project description:Transcriptome of 17 tru-cut biopsies and 13 matched surgical samples from ER+ breast tumor patients, treated for 3 months with Anastrozole were anayzed to identify a robust expression signature predictive of response to Anastrozole neoadjuvant treatment in ER+ breast cancer patients and, at the same time, to delineate treatment effects.

2010-05-17 | GSE18378 | GEO

Respiratory Health Outcomes in Neonates (RHiNO) Study Urine Proteomics

Project description:Urine sampled from preterm-born (<34 weeks gestation) school-aged (7-12yrs) children and term born (>/=37 weeks gestation). Spirometry, exercise testing and cardiovascular assessment performed at time of sampling. Preter-born children with low lung function entered a randomised placebo controlled trial of inhaler therapies.

2023-07-31 | PXD042759 | Pride

Zinc supplementation with or without additional micronutrients does not affect peripheral blood gene expression or serum cytokine level in Bangladeshi children

Project description:Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterised. We sought to define the effect of zinc supplementation on peripheral blood gene expression among young children in Dhaka, Bangladesh. In a sub study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks 1) MNPs containing 10 mg of zinc; 2) dispersible tablet containing 10 mg zinc; or 3) placebo powder, we used RNA-sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial. We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of intervention, or an effect from intervention on change in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) on peripheral blood gene expression.

2021-10-27 | GSE184998 | GEO

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