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ESR1 and breast

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https://www.readbyqxmd.com/read/29780747/precision-medicine-in-hormone-receptor-positive-breast-cancer
#1
REVIEW
Azadeh Nasrazadani, Roby A Thomas, Steffi Oesterreich, Adrian V Lee
In recent decades, breast cancer has become largely manageable due to successes with hormone receptor targeting. Hormone receptor-positive tumors have favorable outcomes in comparison to estrogen receptor (ESR1, ER)/progesterone receptor-negative tumors given the targetable nature of these tumors, as well as their inherently less aggressive character. Nonetheless, treatment resistance is frequently encountered due to a variety of mechanisms, including ESR1 mutations and loss of ER expression. A new era of precision medicine utilizes a range of methodologies to allow real-time analysis of individual genomic signatures in metastases and liquid biopsies with the goal of finding clinically actionable targets...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29769099/circulating-esr1-mutations-at-the-end-of-aromatase-inhibitor-adjuvant-treatment-and-after-relapse-in-breast-cancer-patients
#2
Violette Allouchery, Ludivine Beaussire, Anne Perdrix, David Sefrioui, Laetitia Augusto, Cécile Guillemet, Nasrin Sarafan-Vasseur, Frédéric Di Fiore, Florian Clatot
BACKGROUND: Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. METHODS: This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29763890/mir-301a-3p-suppresses-estrogen-signaling-by-directly-inhibiting-esr1-in-er%C3%AE-positive-breast-cancer
#3
Sandra Lettlova, Veronika Brynychova, Jan Blecha, David Vrana, Magdalena Vondrusova, Pavel Soucek, Jaroslav Truksa
BACKGROUND/AIMS: MiRNA-301a-3p is an oncogenic miRNA whose expression is associated with tumor development, metastases and overall poor prognosis. Estrogen receptor α (ERα) is one of the estrogen hormone-activated transcription factors, which regulates a large number of genes and is involved in the mammary gland development. Expression of ERα is considered to be a good indicator for endocrine therapy and breast cancer survival. Loss of ERα in breast cancer patients indicates invasiveness and poor prognosis...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29753772/increase-in-hyaluronic-acid-degradation-decreases-the-expression-of-estrogen-receptor-alpha-in-mcf7-breast-cancer-cell-line
#4
Vincent Hanoux, Judith Eguida, Emmanuelle Fleurot, Jérôme Levallet, Pierre-Jacques Bonnamy
The loss of estrogen receptor α (ERα) expression in breast cancer constitutes a major hallmark of tumor progression to metastasis and is generally correlated to a strong increase in Hyaluronic Acid (HA) turnover. The aim of our study was to search for a putative link between these two major events of breast cancer progression in the estrogen receptor-positive (ER+) MCF7 breast cancer cell line. The increase in HA turnover was performed by stable overexpression of the standard CD44 (CD44S) isoform and also by treatment with exogenous Hyaluronidase (Hyal) to allow an increase in HA catabolism...
May 10, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29748621/proteomic-profiling-identifies-key-coactivators-utilized-by-mutant-er%C3%AE-proteins-as-potential-new-therapeutic-targets
#5
Leah A Gates, Guowei Gu, Yue Chen, Aarti D Rohira, Jonathan T Lei, Ross A Hamilton, Yang Yu, David M Lonard, Jin Wang, Shu-Ping Wang, David G Edwards, Philip F Lavere, Jiangyong Shao, Ping Yi, Antrix Jain, Sung Yun Jung, Anna Malovannaya, Shunqiang Li, Jieya Shao, Robert G Roeder, Matthew J Ellis, Jun Qin, Suzanne A W Fuqua, Bert W O'Malley, Charles E Foulds
Approximately 75% of breast cancers are estrogen receptor alpha (ERα)-positive and are treatable with endocrine therapies, but often patients develop lethal resistant disease. Frequent mutations (10-40%) in the ligand-binding domain (LBD) codons in the gene encoding ERα (ESR1) have been identified, resulting in ligand-independent, constitutively active receptors. In addition, ESR1 chromosomal translocations can occur, resulting in fusion proteins that lack the LBD and are entirely unresponsive to all endocrine treatments...
May 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29736566/the-impact-of-esr1-mutations-on-the-treatment-of-metastatic-breast-cancer
#6
REVIEW
Sasha M Pejerrey, Derek Dustin, Jin-Ah Kim, Guowei Gu, Yassine Rechoum, Suzanne A W Fuqua
After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene...
May 7, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29731982/gene-specific-methylation-profiles-in-brca-mutation-positive-and-brca-mutation-negative-male-breast-cancers
#7
Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29718092/updated-results-from-monaleesa-2-a-phase-iii-trial-of-first-line-ribociclib-plus-letrozole-versus-placebo-plus-letrozole-in-hormone-receptor-positive-her2-negative-advanced-breast-cancer
#8
G N Hortobagyi, S M Stemmer, H A Burris, Y S Yap, G S Sonke, S Paluch-Shimon, M Campone, K Petrakova, K L Blackwell, E P Winer, W Janni, S Verma, P Conte, C L Arteaga, D A Cameron, S Mondal, F Su, M Miller, M Elmeliegy, C Germa, J O'Shaughnessy
Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. Patients and methods: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2...
April 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29713003/multi-omics-profiling-of-younger-asian-breast-cancers-reveals-distinctive-molecular-signatures
#9
Zhengyan Kan, Ying Ding, Jinho Kim, Hae Hyun Jung, Woosung Chung, Samir Lal, Soonweng Cho, Julio Fernandez-Banet, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Yoon-La Choi, Shibing Deng, Ji-Yeon Kim, Jin Seok Ahn, Ying Sha, Xinmeng Jasmine Mu, Jae-Yong Nam, Young-Hyuck Im, Soohyeon Lee, Woong-Yang Park, Seok Jin Nam, Yeon Hee Park
Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA...
April 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29702197/mutations-in-the-estrogen-receptor-alpha-hormone-binding-domain-promote-stem-cell-phenotype-through-notch-activation-in-breast-cancer-cell-lines
#10
L Gelsomino, S Panza, C Giordano, I Barone, G Gu, E Spina, S Catalano, S Fuqua, S Andò
The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behaviour of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44+ /CD24- ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities...
April 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29689710/esr1-and-pik3ca-mutational-status-in-serum-and-plasma-from-metastatic-breast-cancer-patients-a-comparative-study
#11
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Hirotaka Iwase
PURPOSE: Plasma and serum cell-free DNA (cfDNA) are useful sources of tumor DNA, but comparative investigations of the tumor mutational status between them are rare. METHODS: we performed droplet digital PCR assay for representative hotspot mutations in metastatic breast cancer (MBC) (ESR1 and PIK3CA) in serum and plasma cfDNA concurrently extracted from the blood of 33 estrogen receptor-positive MBC patients. RESULTS: ESR1 mutations in plasma cfDNA were found in 7 of the 33 patients; ESR1 mutations in serum cfDNA were detected in only one out of 7 patients with ESR1 mutations in plasma cfDNA...
April 7, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29687853/lncrna-linc01116-competes-with-mir-145-for-the-regulation-of-esr1-expression-in-breast-cancer
#12
H-B Hu, Q Chen, S-Q Ding
OBJECTIVE: To investigate the biological role and clinical significance of long non-coding RNAs (lncRNA) LINC01116 in breast cancer. MATERIALS AND METHODS: In the public database Gene Expression Omnibus (GEO), the breast cancer data set GSE54002 was screened for differentially expressed lncRNA LINC01116 in breast cancer tissues and paracancerous tissues. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01116 in 64 breast cancer tissues and 30 normal breast tissues...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29685157/estrogen-induced-mir-196a-elevation-promotes-tumor-growth-and-metastasis-via-targeting-spred1-in-breast-cancer
#13
Cheng-Fei Jiang, Zhu-Mei Shi, Dong-Mei Li, Ying-Chen Qian, Yi Ren, Xiao-Ming Bai, Yun-Xia Xie, Lin Wang, Xin Ge, Wei-Tao Liu, Lin-Lin Zhen, Ling-Zhi Liu, Bing-Hua Jiang
BACKGROUND: Estrogen plays a critical role in breast cancer (BC) progression through estrogen receptor (ER)-mediated gene regulation. Emerging studies suggest that the malignant progress of BC cells is influenced by the cross talk between microRNAs (miRNAs) and ER-α signaling. However, the mechanism and functional linkage between estrogen and miRNAs remain unclear. METHODS: The expression levels of miR-196a and SPRED1 in BC were tested by qRT-PCR in 46 paired BC and adjacent tissues and by the GEO datasets...
April 23, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29666928/implications-of-esr1-mutations-in-hormone-receptor-positive-breast-cancer
#14
REVIEW
Tomás Reinert, Rodrigo Gonçalves, José Bines
Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment...
April 17, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29662653/plasma-thymidine-kinase-1-activity-predicts-outcome-in-patients-with-hormone-receptor-positive-and-her2-negative-metastatic-breast-cancer-treated-with-endocrine-therapy
#15
Martina Bonechi, Francesca Galardi, Chiara Biagioni, Francesca De Luca, Mattias Bergqvist, Magnus Neumüller, Cristina Guarducci, Giulia Boccalini, Stefano Gabellini, Ilenia Migliaccio, Angelo Di Leo, Marta Pestrin, Luca Malorni
The aim of this study was to investigate if thymidine kinase-1 (TK1), a well-known proliferation marker, could represent a valid circulating biomarker to identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic breast cancer (MBC) patients most likely to benefit from endocrine therapy (ET). We used the DiviTum™ assay to analyze TK1 activity in cell lysates of three HR+/HER2neg BC cell lines and in plasma of 31 HR+/HER2neg MBC patients receiving ET. Blood samples were collected at treatment initiation, after one month and at disease progression...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29659014/single-cpg-hypermethylation-allele-methylation-errors-and-decreased-expression-of-multiple-tumor-suppressor-genes-in-normal-body-cells-of-mutation-negative-early-onset-and-high-risk-breast-cancer-patients
#16
Julia Böck, Silke Appenzeller, Larissa Haertle, Tamara Schneider, Andrea Gehrig, Jörg Schröder, Simone Rost, Beat Wolf, Claus R Bartram, Christian Sutter, Thomas Haaf
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age-matched controls...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29629944/human-endometriosis-tissue-microarray-reveals-site-specific-expression-of-estrogen-receptors-progesterone-receptor-and-ki67
#17
Mariano Colón-Caraballo, Miosotis García, Adalberto Mendoza, Idhaliz Flores
Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA)...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29620220/translational-control-of-the-undifferentiated-phenotype-in-er%C3%A2-positive-breast-tumor-cells-cytoplasmic-localization-of-er%C3%AE-and-impact-of-ires-inhibition
#18
Christos Vaklavas, Kurt R Zinn, Sharon L Samuel, Zheng Meng, William E Grizzle, Hyoungsoo Choi, Scott W Blume
Using a series of potential biomarkers relevant to mechanisms of protein synthesis, we observed that estrogen receptor (ER)-positive breast tumor cells exist in two distinct yet interconvertible phenotypic states (of roughly equal proportion) which differ in the degree of differentiation and use of IRES-mediated translation. Nascently translated IGF1R in the cytoplasm positively correlated with IRES activity and the undifferentiated phenotype, while epitope accessibility of RACK1, an integral component of the 40S ribosomal subunit, aligned with the more differentiated IRES-off state...
March 23, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29609951/bone-metastasis-in-advanced-breast-cancer-analysis-of-gene-expression-microarray
#19
Irawan Cosphiadi, Tubagus D Atmakusumah, Nurjati C Siregar, Abdul Muthalib, Alida Harahap, Muchtarruddin Mansyur
BACKGROUND: Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. PATIENTS AND METHODS: A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study...
March 8, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29605850/the-pancancer-dna-methylation-trackhub-a-window-to-the-cancer-genome-atlas-epigenomics-data
#20
Izaskun Mallona, Alberto Sierco, Miguel A Peinado
The Cancer Genome Atlas (TCGA) epigenome data includes the DNA methylation status of tumor and normal tissues of large cohorts for dozens of cancer types. Due to the moderately large data sizes, retrieving and analyzing them requires basic programming skills. Simple data browsing (e.g., candidate gene search) is hampered by the scarcity of easy-to-use data browsers addressed to the broad community of biomedical researchers. We propose a new visualization method depicting the overall DNA methylation status at each TCGA cohort while emphasizing its heterogeneity, thus facilitating the evaluation of the cohort variability and the normal versus tumor differences...
2018: Methods in Molecular Biology
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