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ESR1 and breast

Alan R Gilmore, Matthew Alderdice, Kienan I Savage, Paul G O'Reilly, Aideen C Roddy, Philip D Dunne, Mark Lawler, Simon S McDade, David J Waugh, Darragh G McArt
Modern methods of acquiring molecular data have improved rapidly in recent years, making it easier for researchers to collect large volumes of information. However, this has increased the challenge of recognizing interesting patterns within the data. Atlas Correlation Explorer (ACE) is a user-friendly workbench for seeking associations between attributes in the cancer genome atlas (TCGA) database. It allows any combination of clinical and genomic data streams to be searched using an evolutionary algorithm approach...
February 13, 2019: Cancer Research
Behzad Mansoori, Ali Mohammadi, Morten F Gjerstorff, Solmaz Shirjang, Zahra Asadzadeh, Vahid Khaze, Uffe Holmskov, Tohid Kazemi, Pascal H G Duijf, Behzad Baradaran
Estrogen receptors (ERs) are involved in the development of many types of malignant tumors, in particular, breast cancer. Among others, ERs affect cell growth, proliferation, and differentiation. The microRNA (miRNA) miR-142-3p has been shown to inhibit carcinogenesis by regulating various cellular processes, including cell cycle progression, cell migration, apoptosis, and invasion. It does so via targeting molecules involved in a range of signaling pathways. We surgically collected 20 ER-positive breast cancer samples, each with matched adjacent normal breast tissue, and measured the expression of miR-142-3p via quantitative real-time polymerase chain reaction (qRT-PCR)...
February 11, 2019: Journal of Cellular Physiology
Nicholas G Smith, Rekha Gyanchandani, Osama S Shah, Grzegorz T Gurda, Peter C Lucas, Ryan J Hartmaier, Adam M Brufsky, Shannon Puhalla, Amir Bahreini, Karthik Kota, Abigail I Wald, Yuri E Nikiforov, Marina N Nikiforova, Steffi Oesterreich, Adrian V Lee
BACKGROUND: Breast cancer is the most common invasive cancer among women worldwide. Next-generation sequencing (NGS) has revolutionized the study of cancer across research labs around the globe; however, genomic testing in clinical settings remains limited. Advances in sequencing reliability, pipeline analysis, accumulation of relevant data, and the reduction of costs are rapidly increasing the feasibility of NGS-based clinical decision making. METHODS: We report the development of MammaSeq, a breast cancer-specific NGS panel, targeting 79 genes and 1369 mutations, optimized for use in primary and metastatic breast cancer...
February 8, 2019: Breast Cancer Research: BCR
Lotem Zinger, Keren Merenbakh-Lamin, Anat Klein Goldberg, Adi Elazar, Shani Journo, Tomer Boldes, Metsada Pasmanik-Chor, Avishay Spitzer, Tamar Rubinek, Ido Wolf
PURPOSE: Mutations in the ligand binding domain (LBD) of estrogen receptor α (ER) confer constitutive transcriptional activity and resistance to endocrine therapies in breast cancer patients. Accumulating clinical data suggest adverse outcome for patients harboring tumors expressing these mutations. We aimed to elucidate mechanisms conferring this aggressive phenotype. EXPERIMENTAL DESIGN: Cells constitutively expressing physiologic levels of ER harboring activating LBD mutations were generated and characterized for viability, invasiveness and tumor formation in vivo...
February 7, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kaifeng Deng, Shanying Mo, Xuexiang Liu, Jifei Chen, Qiaoyun Zhang, Xiaoli Chen, Jianming Chen, Shengming Dai
BACKGROUND: Based on estrogen active substances, many women consume soy foods in the belief that it could prevent breast cancer (BC). Women with different molecular subtypes would be likely to have diverse reactions to soy foods, especially those with the estrogen-receptor-positive (ER+ ) subtype. The aim of the current study is to identify the differentially expressed genes (DEGs) on soy foods in premenopausal patients with Lumina A subtype of BC (LABC) after soy food treatment, and to further investigate the critical molecule change...
December 12, 2018: Clinical Breast Cancer
R Condorelli, F Mosele, B Verret, T Bachelot, P L Bedard, J Cortes, D M Hyman, D Juric, I Krop, I Bieche, C Saura, C Sotiriou, F Cardoso, S Loibl, F Andre, N C Turner
Better knowledge of the tumor genomic landscapes has helped to develop more effective targeted drugs. However, there is no tool to interpret targetability of genomic alterations assessed by next generation sequencing in the context of clinical practice. Our aim is to rank the level of evidence of individual recurrent genomic alterations observed in breast cancer based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) in order to help the clinicians to prioritize treatment. Analyses of databases suggested that there are around 40 recurrent driver alterations in breast cancer...
January 31, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Huiru Chang, Song Yao, David Tritchler, Meredith A Hullar, Johanna W Lampe, Lilian U Thompson, Susan E McCann
Background: Metabolism and excretion of the phytoestrogen enterolactone (ENL), which has been associated with breast cancer risk, may be affected by variation in steroid hormone and xenobiotic-metabolizing genes. Methods: We conducted a randomized, crossover flaxseed intervention study in 252 healthy, postmenopausal women [137 European ancestry (EA) and 115 African ancestry (AA)] from western New York. Participants were randomly assigned to maintain usual diet or consume 10 g/day ground flaxseed for 6 weeks...
February 1, 2019: Cancer Epidemiology, Biomarkers & Prevention
Ornella I Selmin, Micah G Donovan, Bethany Skovan, Gillian D Paine-Murieta, Donato F Romagnolo
A significant percentage (~30%) of estrogen receptor‑α (ERα)‑positive tumors become refractory to endocrine therapies; however, the mechanisms responsible for this resistance remain largely unknown. Chronic exposure to arsenic through foods and contaminated water has been linked to an increased incidence of several tumors and long‑term health complications. Preclinical and population studies have indicated that arsenic exposure may interfere with endocrine regulation and increase the risk of breast tumorigenesis...
January 15, 2019: International Journal of Oncology
Sayem Miah, Edward Bagu, Raghuveera Goel, Yetunde Ogunbolude, Chenlu Dai, Alison Ward, Frederick S Vizeacoumar, Gerald Davies, Franco J Vizeacoumar, Deborah Anderson, Kiven Erique Lukong
BACKGROUND: BRK is, a non-receptor tyrosine kinase, overexpressed in approximately 85% of human invasive ductal breast tumors. It is not clear whether BRK expression correlates with breast cancer subtypes, or the expression has prognostic or diagnostic significance. Herein, we investigated the correlation of BRK with any breast cancer subtypes and clinicopathological significance of BRK expression in breast cancer. METHODS: In this study, we examined BRK expression in 120 breast tumor samples and 29 breast cancer cell lines to explore the positive correlation between BRK and the expression of ERα...
January 16, 2019: BMC Cancer
Tomohiro Shibata, Eriko Tokunaga, Satoshi Hattori, Kosuke Watari, Yuichi Murakami, Nami Yamashita, Eiji Oki, Junji Itou, Masakazu Toi, Yoshihiko Maehara, Michihiko Kuwano, Mayumi Ono
The enhanced expression of the Y-box binding protein YBX1 is consistently correlated with poor outcomes or reduced survival of breast cancer patients. However, the mechanism underlying the association between increased YBX1 expression and poor outcomes has yet to be revealed. We searched a database for the top 500 genes that are positively or negatively correlated with YBX1 and with ESR1 in breast cancer patients. We further examined the association between YBX1-correlated genes and breast cancer outcomes in patients at Kyushu University Hospital...
December 14, 2018: Oncotarget
Jingyu Liu, Jing Li, Hui Wang, Yikai Wang, Qiongzhi He, Xuefeng Xia, Zhe-Yu Hu, Quchang Ouyang
BACKGROUND: Among breast cancer (BC) patients, near 40% are post-menopause, and 70%-80% are hormone receptor (HR)-positive. About 30%-40% BC patients who are diagnosed as invasive carcinoma HR-positive BC would eventually develop metastatic breast cancers. In 2016, FALCON trial proves Fulvestrant as an effective first-line endocrine therapy for post-menopause HR-positive advanced BC (ABC) patients. But even after FALCON published, Fulvestrant is rarely used as first-line in real world ABC patients in China...
January 15, 2019: Journal of Translational Medicine
Zhijun Dai, Tian Tian, Meng Wang, Tielin Yang, Hongtao Li, Shuai Lin, Qian Hao, Peng Xu, Yujiao Deng, Linghui Zhou, Na Li, Yan Diao
Background: Estrogen exposure is a widely known risk factor for BC. And the interaction of estrogen with estrogen receptor (ER) plays an important role in breast cancer development. This case-control study aims to assess the association of genetic polymorphisms in the estrogen receptor genes with breast cancer (BC) susceptibility in Chinese Han women. Methods: Four polymorphisms (rs2881766, rs9383951, rs9340799 in ESR1 and rs3020449 in ESR2 ) were genotyped in 459 patients and 549 healthy controls using the Sequenom MassARRAY method...
2019: Cancer Cell International
Dan He, Xiao Wang, Yan Zhang, Jian Zhao, Rui Han, Ying Dong
BACKGROUND: DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer. ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors. However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively. The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR expression...
January 3, 2019: Chinese Medical Journal
Sherri Z Millis, Denis L Jardim, Lee Albacker, Jeffrey S Ross, Vincent A Miller, Siraj M Ali, Razelle Kurzrock
BACKGROUND: The phosphatidylinositol 3-kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co-alterations serving as potential resistance/attenuation mechanisms. METHODS: Consecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment-certified laboratory using comprehensive genomic profiling performed by next-generation sequencing (315 genes). The co-alterations evaluated included the Erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, RAS, MET proto-oncogene tyrosine kinase (MET), and mitogen-activated protein kinase kinase (MAP2K) genes as well as tumor protein 53 (TP53), estrogen receptor 1 (ESR1), and androgen receptor (AR)...
December 24, 2018: Cancer
Shuang G Zhao, William S Chen, Rajdeep Das, S Laura Chang, Scott A Tomlins, Jonathan Chou, David A Quigley, Ha X Dang, Travis J Barnard, Brandon A Mahal, Ewan A Gibb, Yang Liu, Elai Davicioni, Linda R Duska, Edwin M Posadas, Shruti Jolly, Daniel E Spratt, Paul L Nguyen, Christopher A Maher, Eric J Small, Felix Y Feng
BACKGROUND: Carcinomas originate from epithelial tissues, which have apical (luminal) and basal orientations. The degree of luminal versus basal differentiation in cancer has been shown to be biologically important in some carcinomas and impacts treatment response. EXPERIMENTAL DESIGN: While prior studies have focused on individual cancer types, we used a modified clinical-grade classifier (PAM50) to subtype 8764 tumors across 22 different carcinomas into luminal A, luminal B, and basal-like tumors...
December 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elena Lopez-Knowles, Alex Pearson, Gene Schuster, Pascal Gellert, Ricardo Ribas, Belinda Yeo, Ros Cutts, Richard Buus, Isaac Garcia-Murillas, Ben Haynes, Lesley-Ann Martin, Ian Smith, Nick Turner, Mitch Dowsett
BACKGROUND: Several thousand breast cancer patients develop resistance to aromatase inhibitors (AIs) each year in the UK. Rational treatment requires an improved molecular characterisation of resistant disease. MATERIALS AND METHODS: The mutational landscape of 198 regions in 16 key breast cancer genes and RNA expression of 209 genes covering key pathways was evaluated in paired biopsies before AI treatment and at progression on AI from 48 patients. Validity of findings was assessed in another five ESR1-mutated tumours progressing on AI...
December 19, 2018: British Journal of Cancer
François Le Dily, Enrique Vidal, Yasmina Cuartero, Javier Quilez, A Silvina Nacht, Guillermo P Vicent, José Carbonell-Caballero, Priyanka Sharma, José Luis Villanueva-Cañas, Roberto Ferrari, Lara Isabel De Llobet, Gaetano Verde, Roni H G Wright, Miguel Beato
In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites, hereafter called hormone-control regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ESR1 and PGR...
December 14, 2018: Genome Research
Sunil Kumar, Daniel Lindsay, Q Brent Chen, Amy L Garrett, Xianming M Tan, Carey K Anders, Lisa A Carey, Gaorav P Gupta
Serial monitoring of plasma DNA mutations in estrogen receptor positive metastatic breast cancer (ER + MBC) holds promise as an early predictor of therapeutic response. Here, we developed dPCR-SEQ, a customized assay that utilizes digital PCR-based target enrichment followed by next-generation sequencing to analyze plasma DNA mutations in ESR1 , PIK3CA , and TP53 . We validated dPCR-SEQ in a prospective cohort of 58 patients with ER + MBC and demonstrate excellent concordance with hotspot ESR1 mutation abundance measured by conventional digital PCR...
2018: NPJ Breast Cancer
Jonathan T Lei, Xuxu Gou, Matthew J Ellis
Estrogen receptor alpha gene ( ESR1 ) fusion transcripts have been identified in breast cancer but their role in breast cancer is not completely understood. Here, we report a causal role for ESR1 fusions in driving both endocrine therapy resistance and metastasis, and describe a therapeutic strategy to target ESR1 fusion-induced growth.
2018: Molecular & Cellular Oncology
Sean W Fanning, Rinath Jeselsohn, Venkatasubramanian Dharmarajan, Christopher G Mayne, Mostafa Karimi, Gilles Buchwalter, René Houtman, Weiyi Toy, Colin E Fowler, Ross Han, Muriel Lainé, Kathryn E Carlson, Teresa A Martin, Jason Nowak, Jerome C Nwachukwu, David J Hosfield, Sarat Chandarlapaty, Emad Tajkhorshid, Kendall W Nettles, Patrick R Griffin, Yang Shen, John A Katzenellenbogen, Myles Brown, Geoffrey L Greene
Acquired resistance to endocrine therapy remains a significant clinical burden for breast cancer patients. Somatic mutations in the ESR1 (estrogen receptor alpha (ERα)) gene ligand-binding domain (LBD) represent a recognized mechanism of acquired resistance. Antiestrogens with improved efficacy versus tamoxifen might overcome the resistant phenotype in ER+ breast cancers. Bazedoxifene (BZA) is a potent antiestrogen that is clinically approved for use in hormone replacement therapies. We found that BZA possesses improved inhibitory potency against the Y537S and D538G ERα mutants compared to tamoxifen and has additional inhibitory activity in combination with the CDK4/6 inhibitor palbociclib...
November 29, 2018: ELife
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