Transcription profiling of human breast cancer biopsies taken before and after patients were treated with aromatase inhibitors
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mackay A
PROVIDER: S-ECPF-TABM-180 | biostudies-other | 2007
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Molecular response to Aromatase Inhibitor Treatment in Primary Breast Cancer
2007-11-29 | E-TABM-180 | biostudies-arrayexpress
Project description:Analysis of breast cancer tumors following fulvestrant treatment for 4 weeks. Fulvestrant is a highly specific ER antagonist used to treat postmenopausal women with breast cancer. Data provide insight into the molecular mechanism of action of fulvestrant on whole genome expression.
| S-ECPF-MTAB-887 | biostudies-other
Project description:Aromatase inhibitors (AI) are extensively used in the treatment of estrogen receptor-positive breast cancers, however resistance to AI treatment is commonly observed. Apart from Estrogen receptor (ERα) expression, no predictive biomarkers for response to AI treatment are clinically applied. Yet, since other therapeutic options exist in the clinic, such as tamoxifen, there is an urgent medical need for the development of treatment-selective biomarkers, enabling personalized endocrine treatment selection in breast cancer. In the described dataset, ERα chromatin binding and histone marks H3K4me3 and H3K27me3 were assessed in a genome-wide manner by Chromatin Immunoprecipitation (ChIP) combined with massive parallel sequencing (ChIP-seq). These datasets were used to develop a classifier to stratify breast cancer patients on outcome after AI treatment in the metastatic setting. Here we describe in detail the data and quality control metrics, as well as the clinical information associated with the study, published by Jansen et al. [1]. The data is publicly available through the GEO database with accession number GSE40867.
| S-EPMC4536071 | biostudies-literature
Project description:Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to evaluate the occurrence of menopausal symptoms in breast cancer patients receiving the AI therapy. Patients treated with AIs had an increased risk of all-grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14-1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and insomnia in patients receiving AIs was 30.47% (95% CI: 25.51%-35.93%), 17.16% (95% CI: 14%-20.85%), 17.91% (95% CI: 11.29%-27.22%), 14.64% (95% CI: 11.46%-18.52%), and 16.52% (95% CI: 12.45%-21.6 %), respectively. Both arthralgia (RR = 0.34, 95% CI: 0.16-0.75) and sweating (RR = 11.02, 95% CI: 4.11-29.57) differed between patients with early- and advanced-stage breast cancer. Our findings indicates that AIs are associated with a significant risk of developing arthralgia and insomnia in breast cancer patients. Effective early detection and management of menopausal symptoms would likely lead to safer use of AIs in breast cancer patients.
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Project description: Not available
| S-DIXA-D-1147 | biostudies-other
Project description:The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane–based therapy. Tumor tissues from pretreatment needle biopsies from patients enrolled on a paclitaxel/radiation clinical trial were laser capture microdissected for RNA extraction and hybridization to Affymetrix microarrays. We analyzed one array (sample A) from duplicate samples from each patient. 14 subject, 2 replicates each.
| S-ECPF-GEOD-22513 | biostudies-other
Project description:A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.
| S-EPMC4213031 | biostudies-other
Project description:In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation. Experiment Overall Design: biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral
| S-ECPF-GEOD-5462 | biostudies-other
Project description:ContextAromatase deficiency causes obesity and insulin resistance in aromatase knockout mice and humans with rare mutations of the aromatase gene (CYP19). Aromatase inhibitors are a commonly prescribed therapy for postmenopausal breast cancer.ObjectiveWe hypothesized that aromatase inhibitors induce obesity and insulin resistance when used in treatment of breast cancer.DesignCase-control study.SettingUniversity teaching hospital.ParticipantsPatients with postmenopausal breast cancer (n = 20) treated with aromatase inhibitors and 20 age-matched control subjects.Main outcome measuresThe primary outcome measure was insulin sensitivity index - Matsuda, derived from a 75-g oral glucose tolerance test. Body composition was assessed by dual energy x-ray absorptiometry and biopsy specimens of subcutaneous adipose tissue obtained for assessment of mRNA transcript levels. Data are reported as mean ± SEM (patients receiving inhibitors vs control group, respectively).ResultsAromatase inhibitor therapy was associated with significantly lower insulin sensitivity (5.15 ± 0.45 vs 6.80 ± 0.64; P = 0.041), higher peak insulin concentration after oral glucose tolerance test (693.4 ± 78.6 vs 527.6 ± 85.5 pmol/L; P = 0.035), greater percentage of body fat (38.4% ± 1.0% vs 34.6% ± 1.3%; P = 0.026), and higher plasma leptin concentration (23.5 ± 2.8 vs 15.5 ± 2.3 ng/mL; P = 0.035).ConclusionWomen who received aromatase inhibitors for postmenopausal breast cancer had greater percentage body fat and insulin resistance compared with control subjects with no history of breast cancer.
| S-EPMC6642666 | biostudies-literature
Project description:The routine workflow for invasive cancer diagnostics is based on biopsy processing by formalin fixation and subsequent paraffin embedding. Formalin-fixed paraffin-embedded (FFPE) tissue samples are easy to handle, stable and particularly suitable for morphologic evaluation, immunohistochemistry and in situ hybridization. However, it has become a paradigm that these samples cannot be used for genome-wide expression analysis with microarrays. To oppose this view, we present a pilot microarray study using FFPE core needle biopsies from breast cancers as RNA source. We found that microarray probes interrogating sequences near the poly-A-tail of the transcribed genes were well suitable to measure RNA levels in FFPE core needle biopsies. For the ER and the HER2 gene, we observed strong correlations between RNA levels measured in these probe sets and protein expression determined by immunohistochemistry (p = 0.000003 and p = 0.0022). Further, we have identified a signature of 364 genes that correlated with ER protein status and a signature of 528 genes that correlated with HER2 protein status. Many of these genes (ER: 60%) could be confirmed by analysis of an independent publicly available data set. Finally, a hierarchical clustering of the biopsies with respect to three recently reported gene expression grade signatures resulted in widely stable low and high expression grade clusters that correlated with the pathological tumor grade. These findings support the notion that clinically relevant information can be gained from microarray based gene expression profiling of FFPE cancer biopsies. This opens new opportunities for the integration of gene expression analysis into the workflow of invasive cancer diagnostics as well as translational research in the setting of clinical studies. Experiment Overall Design: RNA from 24 breast cancer biopsies extracted with kit A, RNA from 6 breast cancer biopsies extracted with kit B
| S-ECPF-GEOD-11001 | biostudies-other