Database : MEDLINE
Search on : Estrogen and Receptor and alpha [Words]
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[PMID]: 27776265
[Au] Autor:Ianov L; Kumar A; Foster TC
[Ad] Address:Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Genetics and Genomics Program, Genetics Institute, University of Florida, Gainesville, FL, USA.
[Ti] Title:Epigenetic regulation of estrogen receptor α contributes to age-related differences in transcription across the hippocampal regions CA1 and CA3.
[So] Source:Neurobiol Aging;49:79-85, 2017 Jan.
[Is] ISSN:1558-1497
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The expression of estrogen receptor alpha (ERα) varies across brain regions and changes with age and according to the previous history of estradiol exposure. ERα is regulated by a number of mechanisms including the level of mRNA (Esr1) expression. For this study, we took advantage of regional differences in hippocampal ERα expression to investigate DNA ERα promoter methylation at CpG dinucleotide sites as a potential epigenetic mechanism for regulating gene expression. Young and aged female Fischer 344 rats were ovariectomized, and Esr1 expression and ERα promoter methylation were examined in hippocampal regions CA1 and CA3, either 3 or 14 weeks following surgery. The results indicate that reduced Esr1 expression in region CA1 relative to CA3 was associated with an increase in DNA methylation in region CA1, particularly for the first CpG site. Additionally, differential methylation of distal CpG sites, 11-17, was associated with altered Esr1 expression during aging or following long-term hormone deprivation. The results support the idea that methylation of site 1 may be the primary regulatory region for cross-regional patterns in ERα expression, while distal sites are modifiable across the life span and may act as a feedback mechanism for ERα activity.
[Mh] MeSH terms primary: Aging/genetics
Aging/metabolism
CA1 Region, Hippocampal/metabolism
CA3 Region, Hippocampal/metabolism
Epigenesis, Genetic
Estrogen Receptor alpha/genetics
Transcription, Genetic
[Mh] MeSH terms secundary: Animals
DNA Methylation
Estrogen Receptor alpha/metabolism
Female
Gene Expression
Gene Expression Regulation, Developmental/genetics
Rats, Inbred F344
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Estrogen Receptor alpha)
[Em] Entry month:1711
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[Js] Journal subset:IM
[Da] Date of entry for processing:161025
[St] Status:MEDLINE

  2 / 54807 MEDLINE  
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[PMID]: 29522854
[Au] Autor:Fekete C; Vastagh C; Dénes Á; Hrabovszky E; Nyiri G; Kalló I; Liposits Z; Sárvári M
[Ad] Address:Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
[Ti] Title:Chronic amyloid ß oligomer infusion evokes sustained inflammation and microglial changes in the rat hippocampus via NLRP3.
[So] Source:Neuroscience;, 2018 Mar 06.
[Is] ISSN:1873-7544
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Microglia are instrumental for recognition and elimination of amyloid ß oligomers (AßO), but the long-term consequences of AßO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AßO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AßO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AßO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors. Aß plaques were not detectable likely due to microglial elimination of infused oligomers. In addition, we found upregulation of neuronal inhibitory ligands and their cognate microglial receptors, whilst downregulation of Esr1 and Scn1a, encoding estrogen receptor alpha and voltage-gated sodium-channel Na(v)1.1, respectively, was observed. These changes were associated with impaired hippocampus-dependent spatial memory and resembled early neurological changes seen in Alzheimer's disease. To investigate the role of inflammatory actions in memory deterioration, we performed MCC950 infusion, which specifically blocks the NLRP3 inflammasome. MCC950 attenuated AßO-evoked microglia reactivity, restored expression of neuronal inhibitory ligands, reversed downregulation of ERα, and abolished memory impairments. Furthermore, MCC950 abrogated AßO-invoked reduction of serum IL-10. These findings provide evidence that in response to AßO infusion microglia change their phenotype, but the resulting inflammatory changes are sustained for at least one month after the end of AßO challenge. Lasting NLRP3-driven inflammatory alterations and altered hippocampal gene expression contribute to spatial memory decline.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  3 / 54807 MEDLINE  
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[PMID]: 29476880
[Au] Autor:Chen H; Pan J; Zhang L; Chen L; Qi H; Zhong M; Shi X; Du J; Li Q
[Ad] Address:Department of Pharmacy, Huashan Hospital North, Fudan University, Shanghai 201907, China.
[Ti] Title:Downregulation of estrogen-related receptor alpha inhibits human cutaneous squamous cell carcinoma cell proliferation and migration by regulating EMT via fibronectin and STAT3 signaling pathways.
[So] Source:Eur J Pharmacol;825:133-142, 2018 Feb 21.
[Is] ISSN:1879-0712
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Estrogen-related receptor alpha (ERRα), one of orphan nuclear receptors, has been recently revealed as an oncogenic regulator in a variety of cancers. However, the linking gain of ERRα expression and cancer progression in cutaneous squamous cell carcinoma (cSCC) is largely unknown. Here, we showed that the mRNA and protein expression levels of ERRα were markedly higher in A431 cells compared with human keratinocyte cell line HaCaT, and targeted inhibition of ERRα by shRNA or its inverse agonist XCT790 significantly suppressed A431 cells proliferation and migration, while overexpression of ERRα promoted cell proliferation and migration. In addition, the data revealed that ERRα downregulation markedly inhibited the epithelial mesenchymal transition (EMT) of A431 cells with increasing the expression of E-cadherin and decreasing fibronectin (FN) and vimentin. Results from further experiments using Western blot suggested that ERRα suppression inhibited signal transducer and activator of transcription (STAT3) protein expression. In contrast, overexpression of ERRα promoted EMT and the activation of STAT3 pathway. Moreover, treatment with specific STAT3 inhibitor reversed EMT markers in ERRα-overexpressing A431 cells. In tumor xenografts of A431 cells, we further showed that ERRα depletion inhibited cSCC tumor growth in vivo. Taken together, these results demonstrate, for the first time, that ERRα may function as an oncoprotein in cSCC to accelerate tumor aggressiveness by promoting EMT via FN and STAT3 pathway, and it could be a novel target for cSCC therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  4 / 54807 MEDLINE  
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[PMID]: 29414691
[Au] Autor:Ghali RM; Al-Mutawa MA; Al-Ansari AK; Zaied S; Bhiri H; Mahjoub T; Almawi WY
[Ad] Address:Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia; Faculty of Sciences of Bizerte, University of Carthage, Tunisia.
[Ti] Title:Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated features: A case-control study.
[So] Source:Gene;651:194-199, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Estrogen is key to breast cancer pathogenesis, and acts by binding its receptor (ER), which exists as ERα and ERß, encoded by ESR1 and ESR2 genes, respectively. Studies that investigated the association of ESR1 and ESR2 variants with breast cancer yielded mixed outcome, and ethnic contribution was proposed. We evaluated the association between ESR1 and ESR2 variants and breast cancer and associated features in Tunisian women. METHODS: Retrospective case-control study involving 207 female breast cancer patients, and 284 control women. Genotyping was done by real-time PCR. RESULTS: Minor allele frequencies (MAF) of tagging SNPs rs2234693 and rs3798577 (ESR1) were significantly higher, while MAF of rs1256049 (ESR2) was significantly lower in breast cancer patients vs. CONTROLS: Patients carrying rs3798577 genotypes had higher risk, while rs1256049 genotype carriers had reduced risk of breast cancer. The association of ESR1 and ESR2 gene variants with breast cancer depended on ER and Her-2 status. ESR1 rs3798577 and ESR2 rs1256049 were associated with breast cancer in ER-positive cases, and ESR1 rs2234693, and rs3798577 were associated with breast cancer in Her-2-negative cases, while the association of ESR2 rs1256049 with breast cancer was seen in Her-2 positive cases. Haploview analysis identified 4-locus ESR1 haplotypes that were positively (CGTT, TACC, and TACT), and negatively (CGTC) associated with breast cancer. No ESR2 haplotypes associated with breast cancer were identified. CONCLUSION: ESR1 alleles and genotypes, and specific 3-locus ESR1 haplotypes are related with increased breast cancer susceptibility in Tunisian women. However, ESR2 variant and specific 1-locus ESR1 haplotype have a protective effect.
[Mh] MeSH terms primary: Breast Neoplasms/genetics
Estrogen Receptor alpha/genetics
Estrogen Receptor beta/genetics
Polymorphism, Single Nucleotide
[Mh] MeSH terms secundary: Case-Control Studies
Female
Genotyping Techniques
Humans
Middle Aged
Real-Time Polymerase Chain Reaction
Retrospective Studies
Risk Assessment
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (ESR2 protein, human); 0 (Estrogen Receptor alpha); 0 (Estrogen Receptor beta); 0 (estrogen receptor alpha, human)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180208
[St] Status:MEDLINE

  5 / 54807 MEDLINE  
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[PMID]: 29373606
[Au] Autor:Devadas K; Biswas S; Ragupathy V; Lee S; Dayton A; Hewlett I
[Ad] Address:Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States of America.
[Ti] Title:Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
[So] Source:PLoS One;13(1):e0191916, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1ß, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.
[Mh] MeSH terms primary: Estrogens/physiology
HIV/physiology
Macrophages/virology
Progesterone/physiology
Virus Replication
[Mh] MeSH terms secundary: Humans
Polymerase Chain Reaction
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Estrogens); 4G7DS2Q64Y (Progesterone)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191916

  6 / 54807 MEDLINE  
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[PMID]: 29175396
[Au] Autor:Wang F; Liu F; Chen W; Xu R; Wang W
[Ad] Address:School of Biological Science, Luoyang Normal University, Luoyang, 471022, China; Cold Water Fish Breeding Engineering Technology Research Center of Henan Province, Luoyang, 471022, China. Electronic address: wangfan7677@163.com.
[Ti] Title:Effects of triclosan (TCS) on hormonal balance and genes of hypothalamus-pituitary- gonad axis of juvenile male Yellow River carp (Cyprinus carpio).
[So] Source:Chemosphere;193:695-701, 2018 Feb.
[Is] ISSN:1879-1298
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Triclosan (TCS) is a broad spectrum antimicrobial agent which has been widely dispersed and determinated in the aquatic environment. However, the effects of TCS on reproductive endocrine in male fish are poorly understood. In this study, male Yellow River carp (Cyprinus carpio) were exposed to 0, 1/5, 1/10 and 1/20 LC (96 h LC of TCS to carp) TCS under semi-static conditions for 42 d. Vitellogenin (Vtg), 17ß-estradiol (E ), testosterone(T), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-ß, GnRH, estrogen receptor (Er), and androgen receptor (Ar) by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). TCS induced Vtg levels of hepatopancreas, E levels of serum, and inhibited Ar and Er mRNA levels, suggesting that the induction of Vtg production by TCS was indirectly caused by non-Er pathways. TCS-induced Vtg levels by interfering with the reproductive axis at plenty of latent loci of male carps: (a) TCS exposure increased the aromatase mRNA expression of hypothalamus and gonad aromatase, consequently increasing serum concentrations of E to induce Vtg in hepatopancreas; (b) TCS treatment changed GtH-ß and GnRH mRNA expression and secretion, causing the disturbance of reproductive endocrine; (c) TCS exposure decreased Ar mRNA levels, indicating potential Ar-mediated antiandrogen action. These mechanisms showed that TCS may induce Vtg production in male carp by non-Er-mediated pathways.
[Mh] MeSH terms primary: Carps/metabolism
Triclosan/toxicity
Water Pollutants, Chemical/toxicity
[Mh] MeSH terms secundary: Animals
Anti-Infective Agents/toxicity
Aromatase/genetics
Endocrine System/drug effects
Enzyme-Linked Immunosorbent Assay
Estradiol/analysis
Gonadotropin-Releasing Hormone/analysis
Gonadotropin-Releasing Hormone/genetics
Gonads/enzymology
Gonads/metabolism
Hepatopancreas/metabolism
Hormones/metabolism
Hypothalamus/metabolism
Male
Pituitary Gland/metabolism
RNA, Messenger/analysis
Real-Time Polymerase Chain Reaction
Receptors, Estrogen/genetics
Reproduction/drug effects
Testosterone/analysis
Vitellogenins/analysis
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Anti-Infective Agents); 0 (Hormones); 0 (RNA, Messenger); 0 (Receptors, Estrogen); 0 (Vitellogenins); 0 (Water Pollutants, Chemical); 33515-09-2 (Gonadotropin-Releasing Hormone); 3XMK78S47O (Testosterone); 4NM5039Y5X (Triclosan); 4TI98Z838E (Estradiol); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:171128
[St] Status:MEDLINE

  7 / 54807 MEDLINE  
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[PMID]: 28457941
[Au] Autor:Menazza S; Sun J; Appachi S; Chambliss KL; Kim SH; Aponte A; Khan S; Katzenellenbogen JA; Katzenellenbogen BS; Shaul PW; Murphy E
[Ad] Address:Systems Biology Center, National Heart Lung and Blood Institute, NIH, Bethesda, MD, United States.
[Ti] Title:Non-nuclear estrogen receptor alpha activation in endothelium reduces cardiac ischemia-reperfusion injury in mice.
[So] Source:J Mol Cell Cardiol;107:41-51, 2017 Jun.
[Is] ISSN:1095-8584
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Steroid hormone receptors including estrogen receptors (ER) classically function as ligand-regulated transcription factors. However, estrogens also elicit cellular effects through binding to extra-nuclear ER (ERα, ERß, and G protein-coupled ER or GPER) that are coupled to kinases. How extra-nuclear ER actions impact cardiac ischemia-reperfusion (I/R) injury is unknown. We treated ovariectomized wild-type female mice with estradiol or an estrogen-dendrimer conjugate (EDC), which selectively activates extra-nuclear ER, or vehicle interventions for two weeks. I/R injury was then evaluated in isolated Langendorff perfused hearts. Two weeks of treatment with estradiol significantly decreased infarct size and improved post-ischemic contractile function. Similarly, EDC treatment significantly decreased infarct size and increased post-ischemic functional recovery compared to vehicle-treated hearts. EDC also caused an increase in myocardial protein S-nitrosylation, consistent with previous studies showing a role for this post-translational modification in cardioprotection. In further support of a role for S-nitrosylation, inhibition of nitric oxide synthase, but not soluble guanylyl cyclase blocked the EDC mediated protection. The administration of ICI182,780, which is an agonist of G-protein coupled estrogen receptor (GPER) and an antagonist of ERα and ERß, did not result in protection; however, ICI182,780 significantly blocked EDC-mediated cardioprotection, indicating participation of ERα and/or ERß. In studies determining the specific ER subtype and cellular target involved, EDC decreased infarct size and improved functional recovery in mice lacking ERα in cardiomyocytes. In contrast, protection was lost in mice deficient in endothelial cell ERα. Thus, extra-nuclear ERα activation in endothelium reduces cardiac I/R injury in mice, and this likely entails increased protein S-nitrosylation. Since EDC does not stimulate uterine growth, in the clinical setting EDC-like compounds may provide myocardial protection without undesired uterotrophic and cancer-promoting effects.
[Mh] MeSH terms primary: Estrogen Receptor alpha/genetics
Estrogen Receptor beta/genetics
Ischemia/genetics
Reperfusion Injury/genetics
[Mh] MeSH terms secundary: Animals
Endothelium/metabolism
Endothelium/pathology
Estrogen Receptor alpha/antagonists & inhibitors
Estrogen Receptor beta/antagonists & inhibitors
Estrogens/genetics
Estrogens/metabolism
Female
Gene Expression Regulation/drug effects
Humans
Ischemia/metabolism
Ischemia/pathology
Mice
Ovariectomy
Protein Processing, Post-Translational/drug effects
Receptors, Estrogen/antagonists & inhibitors
Receptors, G-Protein-Coupled/antagonists & inhibitors
Reperfusion Injury/metabolism
Reperfusion Injury/pathology
Signal Transduction/drug effects
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Estrogen Receptor alpha); 0 (Estrogen Receptor beta); 0 (Estrogens); 0 (GPR30 protein, mouse); 0 (Receptors, Estrogen); 0 (Receptors, G-Protein-Coupled)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:170502
[St] Status:MEDLINE

  8 / 54807 MEDLINE  
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[PMID]: 29393296
[Au] Autor:Wang Q; Jiang J; Ying G; Xie XQ; Zhang X; Xu W; Zhang X; Song E; Bu H; Ping YF; Yao XH; Wang B; Xu S; Yan ZX; Tai Y; Hu B; Qi X; Wang YX; He ZC; Wang Y; Wang JM; Cui YH; Chen F; Meng K; Wang Z; Bian XW
[Ad] Address:Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
[Ti] Title:Tamoxifen enhances stemness and promotes metastasis of ERα36 breast cancer by upregulating ALDH1A1 in cancer cells.
[So] Source:Cell Res;28(3):336-358, 2018 Mar.
[Is] ISSN:1748-7838
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1038/cr.2018.15

  9 / 54807 MEDLINE  
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[PMID]: 29514843
[Au] Autor:Ricciardelli C; Bianco-Miotto T; Jindal S; Butler LM; Leung S; McNeil CM; O'Toole SA; Ebrahimie E; Millar EKA; Sakko AJ; Ruiz AI; Vowler SL; Hunstman DG; Birrell SN; Sutherland RL; Palmieri C; Hickey T; Tilley WD
[Ad] Address:Adelaide Medical School, University of Adelaide.
[Ti] Title:The Magnitude of Androgen Receptor Positivity in Breast Cancer is Critical for Reliable Prediction of Disease Outcome.
[So] Source:Clin Cancer Res;, 2018 Mar 07.
[Is] ISSN:1078-0432
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer. The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival. EXPERIMENTAL DESIGN: AR positivity was assessed by immunostaining in two clinically-validated primary breast cancer cohorts (training cohort n=219; validation cohort n=418; 77% and 79% estrogen receptor alpha (ERα) positive, respectively). The optimal AR cut-point was determined by ROC analysis in the training cohort and applied to both cohorts. RESULTS: AR was an independent prognostic marker of breast cancer outcome in 22/46 (48%) of previous studies that performed multivariate analyses. Most studies used cut-points of 1% or 10% nuclear positivity. Herein, neither 1 nor 10% cut-points were robustly prognostic. ROC analysis revealed a higher AR cut-point (78% positivity) provided optimal sensitivity and specificity to predict breast cancer survival in the training (HR 0.41, P=0.015) and validation (HR 0.50, P=0.014) cohorts. Ten-fold cross validation confirmed the robustness of this AR cut-point. Patients with ERα positive tumors and AR positivity >78% had the best survival in both cohorts (P<0.0001). Among the combined ERα positive cases, those with comparable or higher levels of AR (AR:ERα positivity ratio >0.87) had the best outcomes (P<0.0001). CONCLUSIONS: This study defines an optimal AR cut-point to reliably predict breast cancer survival. Testing this cut-point in prospective cohorts is warranted for implementation of AR as a prognostic factor in the clinical management of breast cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  10 / 54807 MEDLINE  
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[PMID]: 29315431
[Au] Autor:Schrijver WAME; Suijkerbuijk KPM; van Gils CH; van der Wall E; Moelans CB; van Diest PJ
[Ad] Address:Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
[Ti] Title:Receptor Conversion in Distant Breast Cancer Metastases: A Systematic Review and Meta-analysis.
[So] Source:J Natl Cancer Inst;, 2018 Jan 05.
[Is] ISSN:1460-2105
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: In metastatic breast cancer, hormone and/or human epidermal growth factor receptor 2 (HER2)-targeted therapy decision-making is still largely based on tissue characteristics of the primary tumor. However, a change of estrogen receptor alpha (ERα), progesterone receptor (PR), and HER2 status in distant metastases has frequently been reported. The actual incidence of this phenomenon has been debated. Methods: We performed a meta-analysis including 39 studies assessing receptor conversion from primary breast tumors to paired distant breast cancer metastases. We noted the direction of change (positive to negative or vice versa) and performed subgroup analyses for different thresholds for positivity, the type of test used to assess HER2 receptor status, and metastasis location-specific differences (two-sided tests). Results: Overall, the incidence of receptor conversion varied largely between studies. For ERα, PR, and HER2, we found that random effects pooled positive to negative conversion percentages of 22.5% (95% confidence interval [CI] = 16.4% to 30.0%), 49.4% (95% CI = 40.5% to 58.2%), and 21.3% (95% CI = 14.3% to 30.5%), respectively. Negative to positive conversion percentages were 21.5% (95% CI = 18.1% to 25.5%), 15.9% (95% CI = 11.3% to 22.0%), and 9.5% (95% CI = 7.4% to 12.1%). Furthermore, ERα discordance was statistically significantly higher in the central nervous system and bone compared with liver metastases (20.8%, 95% CI = 15.0% to 28.0%, and 29.3%, 95% CI = 13.0% to 53.5%, vs 14.3%, 95% CI = 11.3% to 18.1, P = .008 and P < .001, respectively), and PR discordance was higher in bone (42.7%, 95% CI = 35.1% to 50.6%, P < .001) and liver metastases (47.0%, 95% CI = 41.0% to 53.0%, P < .001) compared with central nervous system metastases (23.3%, 95% CI = 16.0% to 32.6%). Conclusions: Receptor conversion for ERα, PR, and HER2 occurs frequently in the course of disease progression in breast cancer. Large prospective studies assessing the impact of receptor conversion on treatment efficacy and survival are needed. Meanwhile, reassessing receptor status in metastases is strongly encouraged.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/jnci/djx273


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