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ESR1 and breast

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https://www.readbyqxmd.com/read/30242578/validation-of-the-21-gene-test-as-a-predictor-of-clinical-response-to-neoadjuvant-hormonal-therapy-for-er-her2-negative-breast-cancer-the-transneos-study
#1
Hiroji Iwata, Norikazu Masuda, Yutaka Yamamoto, Tomomi Fujisawa, Tatsuya Toyama, Masahiro Kashiwaba, Shoichiro Ohtani, Naruto Taira, Takehiko Sakai, Yoshie Hasegawa, Rikiya Nakamura, Hiromitsu Akabane, Yukiko Shibahara, Hironobu Sasano, Takuhiro Yamaguchi, Kentaro Sakamaki, Helen Bailey, Diana B Cherbavaz, Debbie M Jakubowski, Naoko Sugiyama, Calvin Chao, Yasuo Ohashi
PURPOSE: The Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole. METHODS: NEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery...
September 21, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30225582/copy-number-profiling-of-oncotype-dx-genes-reveals-association-with-survival-of-breast-cancer-patients
#2
Washaakh Ahmed, Muhammad Faraz Arshad Malik, Muhammad Saeed, Farhan Haq
Copy number variations (CNVs) are key contributors in breast cancer initiation and progression. However, to date, no CNV-based gene signature is developed for breast cancer. 21-gene Oncotype DX, a clinically validated signature, was identified using only RNA expression data in breast cancer patients. In this study, we evaluated whether CNVs of Oncotype DX genes can be used to predict the prognosis of breast cancer patients. Transcriptomic data of 547 and genomic data of 816 of breast cancer patients were downloaded from The Cancer Genome Atlas database...
September 17, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/30214383/microrna-regulation-in-estrogen-receptor-positive-breast-cancer-and-endocrine-therapy
#3
REVIEW
Erin W Howard, Xiaohe Yang
As de novo and acquired resistance to standard first line endocrine therapies is a growing clinical challenge for estrogen receptor-positive (ER+ ) breast cancer patients, understanding the mechanisms of resistance is critical to develop novel therapeutic strategies to prevent therapeutic resistance and improve patient outcomes. The widespread post-transcriptional regulatory role that microRNAs (miRNAs) can have on various oncogenic pathways has been well-documented. In particular, several miRNAs are reported to suppress ERα expression via direct binding with the 3' UTR of ESR1 mRNA, which can confer resistance to estrogen/ERα-targeted therapies...
2018: Biological Procedures Online
https://www.readbyqxmd.com/read/30214302/clinical-utility-of-fulvestrant-in-the-treatment-of-breast-cancer-a-report-on-the-emerging-clinical-evidence
#4
REVIEW
Andrea Rocca, Roberta Maltoni, Sara Bravaccini, Caterina Donati, Daniele Andreis
Fulvestrant is the first selective estrogen receptor (ER) downregulator available in clinical practice. It is a pure antiestrogen with no agonistic effects, leading to degradation of ER alpha, with activity in tamoxifen-resistant breast cancer (BC) models. Pharmacokinetic and pharmacodynamic studies and several postmarketing clinical trials led to the definition of the optimal dose at 500 mg intramuscularly on days 1, 15, and 29 and then every 28 days. Targeting ER alpha, fulvestrant is a cornerstone of treatment in luminal BCs, whose growth is largely driven by the ER pathway...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30211312/genomic-and-expression-profiling-reveal-molecular-heterogeneity-of-disseminated-tumor-cells-in-bone-marrow-of-early-breast-cancer
#5
Mark Jesus M Magbanua, Hope S Rugo, Louai Hauranieh, Ritu Roy, Janet H Scott, Jen Chieh Lee, Feng Hsiao, Eduardo V Sosa, Laura Van't Veer, Laura J Esserman, John W Park
Detection of disseminated tumor cells (DTCs) in bone marrow is an established negative prognostic factor. We isolated small pools of (~20) EPCAM-positive DTCs from early breast cancer patients for genomic profiling. Genome-wide copy number profiles of DTC pools ( n  = 45) appeared less aberrant than the corresponding primary tumors (PT, n  = 16). PIK3CA mutations were detected in 26% of DTC pools ( n  = 53), none of them were shared with matched PTs. Expression profiling of DTC pools ( n  = 30) confirmed the upregulation of EPCAM expression and certain oncogenes (e...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/30194396/variants-associating-with-uterine-leiomyoma-highlight-genetic-background-shared-by-various-cancers-and-hormone-related-traits
#6
Thorunn Rafnar, Bjarni Gunnarsson, Olafur A Stefansson, Patrick Sulem, Andres Ingason, Michael L Frigge, Lilja Stefansdottir, Jon K Sigurdsson, Vinicius Tragante, Valgerdur Steinthorsdottir, Unnur Styrkarsdottir, Simon N Stacey, Julius Gudmundsson, Gudny A Arnadottir, Asmundur Oddsson, Florian Zink, Gisli Halldorsson, Gardar Sveinbjornsson, Ragnar P Kristjansson, Olafur B Davidsson, Anna Salvarsdottir, Asgeir Thoroddsen, Elisabet A Helgadottir, Katrin Kristjansdottir, Orri Ingthorsson, Valur Gudmundsson, Reynir T Geirsson, Ragnheidur Arnadottir, Daniel F Gudbjartsson, Gisli Masson, Folkert W Asselbergs, Jon G Jonasson, Karl Olafsson, Unnur Thorsteinsdottir, Bjarni V Halldorsson, Gudmar Thorleifsson, Kari Stefansson
Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36...
September 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/30182054/-nf1-deficiency-correlates-with-estrogen-receptor-signaling-and-diminished-survival-in-breast-cancer
#7
Patrick S Dischinger, Elizabeth A Tovar, Curt J Essenburg, Zachary B Madaj, Eve E Gardner, Megan E Callaghan, Ashley N Turner, Anil K Challa, Tristan Kempston, Bryn Eagleson, Robert A Kesterson, Roderick T Bronson, Megan J Bowman, Carrie R Graveel, Matthew R Steensma
The key negative regulatory gene of the RAS pathway, NF1 , is mutated or deleted in numerous cancer types and is associated with increased cancer risk and drug resistance. Even though women with neurofibromatosis (germline NF1 mutations) have a substantially increased breast cancer risk at a young age and NF1 is commonly mutated in sporadic breast cancers, we have a limited understanding of the role of NF1 in breast cancer. We utilized CRISPR-Cas9 gene editing to create Nf1 rat models to evaluate the effect of Nf1 deficiency on tumorigenesis...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/30173322/esr1-promoter-methylation-status-in-primary-breast-cancer-and-its-corresponding-metastases
#8
Verena Kirn, Leonie Strake, Fabinshy Thangarajah, Lisa Richters, Hannah Eischeid, Ulrike Koitzsch, Margarete Odenthal, Jochen Fries
The role of ESR1 methylation in breast cancer and its influence on disease progression is not yet fully understood. Healthy breast tissue usually does not show ESR1 promoter methylation, whereas the frequency of ESR1 methylation appears to increase in primary breast cancer and in metastatic disease. Although women with ER positive breast cancer have a good prognosis, some will relapse. We aimed to evaluate the methylation status of ESR1 in primary breast cancer and its corresponding metastases by a methylation-specific real-time PCR and to correlate the methylation status with clinical outcome...
September 1, 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/30165855/transforming-growth-factor-beta1-targets-estrogen-receptor-signaling-in-bronchial-epithelial-cells
#9
L Cody Smith, Santiago Moreno, Lauren Robertson, Sarah Robinson, Kristal Gant, Andrew J Bryant, Tara Sabo-Attwood
BACKGROUND: Sex differences in idiopathic pulmonary fibrosis (IPF) suggest a protective role for estrogen (E2); however, mechanistic studies in animal models have produced mixed results. Reports using cell lines have investigated molecular interactions between transforming growth factor beta1 (TGF-β1) and estrogen receptor (ESR) pathways in breast, prostate, and skin cells, but no such interactions have been described in human lung cells. To address this gap in the literature, we investigated a role for E2 in modulating TGF-β1-induced signaling mechanisms and identified novel pathways impacted by estrogen in bronchial epithelial cells...
August 30, 2018: Respiratory Research
https://www.readbyqxmd.com/read/30158597/immunohistochemical-analysis-of-estrogen-receptor-in-breast-cancer-with-esr1-mutations-detected-by-hybrid-capture-based-next-generation-sequencing
#10
Dara S Ross, Ahmet Zehir, Edi Brogi, Fumiko Konno, Melissa Krystel-Whittemore, Marcia Edelweiss, Michael F Berger, Weiyi Toy, Sarat Chandarlapaty, Pedram Razavi, José Baselga, Hannah Y Wen
Estrogen receptor-α (ER-α), encoded by ESR1, is detected by immunohistochemistry in approximately 70% of invasive breast cancers and serves as a strong predictive biomarker. ESR1-activating mutations in the ligand-binding domain have been reported in up to 35-40% of ER-positive metastatic breast cancers and are associated with endocrine therapy resistance and disease progression. At present, it is unclear whether ESR1 mutations alter the immunohistochemical detection of ER performed in routine clinical practice...
August 29, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/30147360/clinical-value-of-circulating-esr1-mutations-for-patients-with-metastatic-breast-cancer-a-meta-analysis
#11
REVIEW
Kai Zhang, Ruoxi Hong, Fei Xu, Wen Xia, Lee Kaping, Ge Qin, Qiufan Zheng, Qianyi Lu, Yan Xia Shi, Zhong Yu Yuan, Shusen Wang
Background: The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy. Materials and methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30145202/cuedc1-is-a-primary-target-of-er%C3%AE-essential-for-the-growth-of-breast-cancer-cells
#12
Rui Lopes, Gozde Korkmaz, Sonia Aristin Revilla, Romy van Vliet, Remco Nagel, Lars Custers, Yongsoo Kim, Pieter C van Breugel, Wilbert Zwart, Behzad Moumbeini, Zohar Manber, Ran Elkon, Reuven Agami
Breast cancer is the most prevalent type of malignancy in women with ∼1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand-dependent transcription factor. Genome-wide chromatin binding maps suggest that ERα may control the expression of thousands of genes, posing a great challenge in identifying functional targets. Recently, we developed a CRISPR-Cas9 functional genetic screening approach to identify enhancers required for ERα-positive breast cancer cell proliferation...
November 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30139210/derivative-of-stevioside-cpuk02-restores-esr1-gene-methylation-in-mda-mb-231
#13
Saeed Khazayel, Pooneh Mokarram, Zeinab Mohammadi, Fatemeh Ramezani, Zhang Dayong
Background: CPUK02 (15-Oxosteviol benzyl ester) is a new ent-kaurenoid derivative of stevioside and exhibits strong anti-cancer activity. Nowadays, the pattern of epigenetic in cancer has been topic of many studies and DNA methylation targeting represents a relevant strategy for cancer treatment. Since, no study conducted to this mechanism, we attempt to evaluate whether CPUK02 induce its anti-cancer effects via alteration the level of mRNA DNMT3B, DNMT3A expression and ESR1 methylation pattern in breast cancer cells line...
August 24, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/30125992/transcriptome-mining-of-non-brca1-a2-and-brca1-a2-familial-breast-cancer
#14
Vahid Akbari, Marzieh Kallhor, Mohammad Taghi Akbari
About 10% of all breast cancer cases are the familial type. Mutations in two highly penetrance breast cancer susceptibility genes, BRCA1 and BRCA2, can only explain 20% to 25% of genetic susceptibility to breast cancer, and most familial breast cancer cases have intact BRCA1 and BRCA2 genes that refer to non-BRCA1/A2 or BRCAX familial breast cancer. Despite extensive studies, more than 50% of genetic susceptibility to breast cancer remained to be disclosed. Finding the differences between these two types of breast cancer (non-BRCA1/A2 and BRCA1/A2) at genomic, transcriptomic, and proteomic levels can help us to elucidate fundamental molecular processes and develope more promising therapeutic targets...
August 20, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30120700/comparison-of-central-laboratory-assessments-of-er-pr-her2-and-ki67-by-ihc-fish-and-the-corresponding-mrnas-esr1-pgr-erbb2-and-mki67-by-rt-qpcr-on-an-automated-broadly-deployed-diagnostic-platform
#15
Natalie C Wu, Wendy Wong, Kenneth E Ho, Victor C Chu, Annaliza Rizo, Simon Davenport, Devon Kelly, Rosemary Makar, Jacek Jassem, Renata Duchnowska, Wojciech Biernat, Barbara Radecka, Tomoyuki Fujita, Jonathan L Klein, Mark Stonecypher, Shoichiro Ohta, Hartmut Juhl, Jodi M Weidler, Michael Bates, Michael F Press
PURPOSE: The methods (IHC/FISH) typically used to assess ER, PR, HER2, and Ki67 in FFPE specimens from breast cancer patients are difficult to set up, perform, and standardize for use in low and middle-income countries. Use of an automated diagnostic platform (GeneXpert®) and assay (Xpert® Breast Cancer STRAT4) that employs RT-qPCR to quantitate ESR1, PGR, ERBB2, and MKi67 mRNAs from formalin-fixed, paraffin-embedded (FFPE) tissues facilitates analyses in less than 3 h. This study compares breast cancer biomarker analyses using an RT-qPCR-based platform with analyses using standard IHC and FISH for assessment of the same biomarkers...
August 17, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30113650/early-onset-complete-ovarian-failure-and-lack-of-puberty-in-a-woman-with-mutated-estrogen-receptor-beta-esr2
#16
Mariarosaria Lang-Muritano, Patrick Sproll, Sascha Wyss, Anne Kolly, Renate Hürlimann, Daniel Konrad, Anna Biason-Lauber
Context: Estrogen resistance due to mutations in the estrogen receptor α (ESR1) was described in men and women and is characterized by osteoporosis, delayed bone age and continuous growth in adulthood, delayed puberty and multiple ovarian cysts in women. Although mutations in ESR2 were found in 46, XY patients with differences of sex development (DSD), no genetic variants of estrogen receptor β (ESR2) were linked to gonadal defects in women. Settings and Patient: Here we describe a 16-year old woman who came to our tertiary care hospital with complete lack of estrogen action, as demonstrated by absent breast development, primary amenorrhea, and osteoporosis, resembling patients with ESR1 mutation...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30104333/a-digital-rna-signature-of-circulating-tumor-cells-predicting-early-therapeutic-response-in-localized-and-metastatic-breast-cancer
#17
Tanya T Kwan, Aditya Bardia, Laura M Spring, Anita Giobbie-Hurder, Mark Kalinich, Taronish Dubash, Tilak Sundaresan, Xin Hong, Joseph A LiCausi, Uyen Ho, Erin J Silva, Ben S Wittner, Lecia V Sequist, Ravi Kapur, David T Miyamoto, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)-derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC-Score after three cycles of neoadjuvant therapy is associated with residual disease at surgery (p=0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC-Score correlates with overall survival (p= 0...
August 13, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30094493/activating-human-epidermal-growth-factor-receptor-2-her2-gene-mutation-in-bone-metastases-from-breast-cancer
#18
Matthias Christgen, Stephan Bartels, Angelina Luft, Sascha Persing, Daniel Henkel, Ulrich Lehmann, Hans Kreipe
In addition to amplification, point mutations of the human epidermal growth factor receptor 2 (HER2) gene (ERBB2) have been shown to activate the corresponding signaling pathway in breast cancer. The prevalence of ERBB2/HER2 mutation in bone metastasis of breast cancer and the associated phenotype are not known. In this study, bone metastases from breast cancer patients (n = 231) were analyzed for ERBB2/HER2 mutation. In 7 patients (3%; median age 70 years, range 50-83 years), gain-of-function mutations of ERBB2/HER2 were detected...
August 9, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/30089255/functional-annotation-of-esr1-gene-fusions-in-estrogen-receptor-positive-breast-cancer
#19
Jonathan T Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W Chan, Jin Cao, Meenakshi Anurag, Purba Singh, Xiaping He, Yoshimasa Kosaka, Ryoichi Matsunuma, Robert Crowder, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Ramalho, Raquel Mary Rodrigues Peres, Nindo Punturi, Cheryl Schmidt, Alex Bartram, Eric Jou, Vaishnavi Devarakonda, Kimberly R Holloway, W Victoria Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan A Parikh, Sherri R Davies, Shunqiang Li, Cynthia X Ma, Vera J Suman, Kelly K Hunt, Mark A Watson, Katherine A Hoadley, E Aubrey Thompson, Xi Chen, Shyam M Kavuri, Chad J Creighton, Christopher A Maher, Charles M Perou, Svasti Haricharan, Matthew J Ellis
RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+ ) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1-6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance...
August 7, 2018: Cell Reports
https://www.readbyqxmd.com/read/30086764/targeted-next-generation-sequencing-identifies-clinically-relevant-somatic-mutations-in-a-large-cohort-of-inflammatory-breast-cancer
#20
Xu Liang, Sophie Vacher, Anais Boulai, Virginie Bernard, Sylvain Baulande, Mylene Bohec, Ivan Bièche, Florence Lerebours, Céline Callens
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients. METHODS: Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients...
August 7, 2018: Breast Cancer Research: BCR
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