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ESR1 and breast

Rong Wang, Jinbin Li, Chunyu Yin, Di Zhao, Ling Yin
BACKGROUND: This study aimed to identify the differentially expressed genes (DEGs) and the typical fusion genes in different types of breast cancers using RNA-seq. METHODS: GSE52643 was downloaded from Gene Expression Omnibus, which included 1 normal sample (MCF10A) and 7 breast cancer samples (BT-474, BT-20, MCF7, MDA-MB-231, MDA-MB-468, T47D, and ZR-75-1). The transcript abundance and the DEGs screening were performed by Cufflinks. The functional and pathway enrichment was analyzed by Gostats...
November 16, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
E S Sokol, Y X Feng, D X Jin, A Basudan, A V Lee, J M Atkinson, J Chen, P J Stephens, G M Frampton, P B Gupta, J S Ross, J Chung, S Oesterreich, S Ali, R J Hartmaier
Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations may develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and Methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 ER-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in 395 cancer-related genes...
November 13, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Claudia Busonero, Stefano Leone, Stefania Bartoloni, Filippo Acconcia
With the advent of omic technologies, our understanding of the molecular mechanisms underlying estrogen receptor α (ERα)-expressing breast cancer (BC) progression has grown exponentially. Nevertheless, the most widely used therapy for inhibiting this disease is endocrine therapy (ET) (i.e., aromatase inhibitors, tamoxifen - Tam, faslodex/fulvestrant - FUL). However, in a considerable number of cases, prolonged patient treatment with ET generates the development of resistant tumor cells and, consequently, tumor relapse, which manifests as metastatic disease that is extremely difficult to manage, especially because such metastatic BCs (MBCs) often express ERα mutations (e...
October 31, 2018: Molecular and Cellular Endocrinology
Kenji Watanabe, Shigeru Yamamoto, Syuiti Sakaguti, Keishiro Isayama, Masaaki Oka, Hiroaki Nagano, Yoichi Mizukami
Breast cancer is the most frequent tumor in women, and in nearly two-thirds of cases, the tumors express estrogen receptor α (ERα, encoded by ESR1). Here, we performed whole-exome sequencing of 16 breast cancer tissues classified according to ESR1 expression and 12 samples of whole blood, and detected 310 somatic mutations in cancer tissues with high levels of ESR1 expression. Of the somatic mutations validated by a different deep sequencer, a novel nonsense somatic mutation, c.2830 C>T; p.Gln944*, in transcriptional regulator switch-independent 3 family member A (SIN3A) was detected in breast cancer of a patient...
October 30, 2018: Scientific Reports
Soni Khandelwal, Mallory Boylan, Julian E Spallholz, Lauren Gollahon
Within the subtypes of breast cancer, those identified as triple negative for expression of estrogen receptor α (ESR1), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), account for 10⁻20% of breast cancers, yet result in 30% of global breast cancer-associated deaths. Thus, it is critical to develop more targeted and efficacious therapies that also demonstrate less side effects. Selenium, an essential dietary supplement, is incorporated as selenocysteine (Sec) in vivo into human selenoproteins, some of which exist as anti-oxidant enzymes and are of importance to human health...
October 26, 2018: International Journal of Molecular Sciences
Ahmed Basudan, Nolan Priedigkeit, Ryan J Hartmaier, Ethan S Sokol, Amir Bahreini, Rebecca J Watters, Michelle M Boisen, Rohit Bhargava, Kurt R Weiss, Maria M Karsten, Carsten Denkert, Jens-Uwe Blohmer, Jose P Leone, Ronald L Hamilton, Adam M Brufsky, Esther Elishaev, Peter C Lucas, Adrian V Lee, Steffi Oesterreich
DNA sequencing has identified a limited number of driver mutations in metastatic breast cancer beyond single base-pair mutations in the estrogen receptor (ESR1). However, our previous studies and others have observed that structural variants, such as ESR1 fusions, may also play a role. Therefore, we expanded upon these observations by performing a comprehensive and highly sensitive characterization of copy number (CN) alterations in a large clinical cohort of metastatic specimens. NanoString DNA hybridization was utilized to measure CN gains, amplifications and deletions of 67 genes in 108 breast cancer metastases, and in 26 cases, the patient-matched primary tumor...
October 24, 2018: Molecular Cancer Research: MCR
Wen Jin, Qian-Zhong Li, Yong-Chun Zuo, Yan-Ni Cao, Lu-Qiang Zhang, Rui Hou, Wen-Xia Su
Breast cancer has a high mortality rate for females. Aberrant DNA methylation plays a crucial role in the occurrence and progression of breast carcinoma. By comparing DNA methylation differences between tumor breast tissue and normal breast tissue, we calculate and analyze the distributions of the hyper- and hypomethylation sites in different function regions. Results indicate that enhancer regions are often hypomethylated in breast cancer. CpG islands (CGIs) are mainly hypermethylated, while the flanking CGI (shores and shelves) is more easily hypomethylated...
October 20, 2018: DNA and Cell Biology
Kerstin Hartmann, Kornelia Schlombs, Mark Laible, Claudia Gürtler, Marcus Schmidt, Ugur Sahin, Hans-Anton Lehr
BACKGROUND: Tissue heterogeneity in formalin-fixed paraffin-embedded (FFPE) breast cancer specimens may affect the accuracy of reverse transcription quantitative real-time PCR (RT-qPCR). Herein, we tested the impact of tissue heterogeneity of breast cancer specimen on the RT-qPCR-based gene expression assay MammaTyper®. METHODS: MammaTyper® quantifies the mRNA expression of the four biomarkers ERBB2, ESR1, PGR, and MKI67. Based on pre-defined cut-off values, this molecular in vitro diagnostic assay permits binary marker classification and determination of breast cancer subtypes as defined by St Gallen 2013...
October 20, 2018: Diagnostic Pathology
Goodwin G Jinesh, Elsa R Flores, Andrew S Brohl
Triple negative breast cancers (TNBCs) are known to express low PGR, ESR1, and ERBB2, and high KRT5, KRT14, and KRT17. However, the reasons behind the increased expressions of KRT5, KRT14, KRT17 and decreased expressions of PGR, ESR1, and ERBB2 in TNBCs are not fully understood. Here we show that, expression of chromosome 19 miRNA cluster (C19MC) specifically marks human TNBCs. Low REST and high CEBPB correlate with expression of C19MC, KRT5, KRT14, and KRT17 and enhancers of these genes/cluster are regulated by CEBPB and REST binding sites...
2018: PloS One
Ju-Han Lee, Hoiseon Jeong, Jung-Woo Choi, Hwa Eun Oh, Young-Sik Kim
BACKGROUND: Liquid biopsies using circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) have been developed for early cancer detection and patient monitoring. To investigate the clinical usefulness of ctDNA aberrations and cfDNA levels in patients with breast cancer (BC), we conducted a meta-analysis of 69 published studies on 5736 patients with BC. METHODS: The relevant publications were identified by searching PubMed and Embase databases. The effect sizes of outcome parameters were pooled using a random-effects model...
October 2018: Medicine (Baltimore)
Jinlei Ding, Xiaonan Wang, Yuan Zhang, Xiaolin Sang, Jingyan Yi, Chongya Liu, Zundong Liu, Min Wang, Nan Zhang, Yijue Xue, Lanlin Shen, Wenzhi Zhao, Fuwen Luo, Pixu Liu, Hailing Cheng
Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ERα-positive (ER+) breast cancer due to the presence of activating PIK3CA mutations. However, recent studies have revealed that increased ERα transcriptional activity limits the efficacy of PI3K inhibitor monotherapy for ER + breast cancers. Herein, we report the identification of BTF3 as an oncogenic transcription factor that regulates ERα expression in luminal breast cancers. Our TCGA analysis reveals high expression levels of BTF3 in luminal/ER + breast cancer and cell line models harboring ERα overexpression...
January 2019: Cancer Letters
Tatsuro Yamamoto, Chiyomi Sakamoto, Hiroaki Tachiwana, Mitsuru Kumabe, Toshiro Matsui, Tadatoshi Yamashita, Masatoshi Shinagawa, Koji Ochiai, Noriko Saitoh, Mitsuyoshi Nakao
Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription...
October 12, 2018: Scientific Reports
Massimo Cristofanilli, Angela DeMichele, Carla Giorgetti, Nicholas C Turner, Dennis J Slamon, Seock-Ah Im, Norikazu Masuda, Shailendra Verma, Sherene Loi, Marco Colleoni, Kathy Puyana Theall, Xin Huang, Yuan Liu, Cynthia Huang Bartlett
BACKGROUND: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. METHODS: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174)...
October 8, 2018: European Journal of Cancer
Xu Liang, Adrien Briaux, Véronique Becette, Camille Benoist, Anais Boulai, Walid Chemlali, Anne Schnitzler, Sylvain Baulande, Sofia Rivera, Marie-Ange Mouret-Reynier, Laurence Venat Bouvet, Thibaut De La Motte Rouge, Jérôme Lemonnier, Florence Lerebours, Céline Callens
BACKGROUND: Postmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis. METHODS: Gene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients...
October 11, 2018: Journal of Hematology & Oncology
Gaetano Verde, Lara I De Llobet, Roni H G Wright, Javier Quilez, Sandra Peiró, François Le Dily, Miguel Beato
Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ERα gene ( ESR1 ) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells...
October 5, 2018: Cancers
Khalid N Al-Zahrani, David P Cook, Barbara C Vanderhyden, Luc A Sabourin
The Androgen Receptor (AR) has recently garnered a lot of attention as a potential biomarker and therapeutic target in hormone-dependent cancers, including breast cancer. However, several inconsistencies exist within the literature as to which subtypes of breast cancer express AR or whether it can be used to define its own unique subtype. Here, we analyze 1246 invasive breast cancer samples from the Cancer Genome Atlas and show that human breast cancers that have been subtyped based on their HER2, ESR1, or PGR expression contain four clusters of genes that are differentially expressed across all subtypes...
September 7, 2018: Oncotarget
Yangfan Du, Na Li, Xin Jiao, Kai Li, Shunchao Yan
Purpose: The predictive ability of plasma ESR1 mutations for outcomes among patients with advanced breast cancer undergoing endocrine therapy (ET) remains disputable. We performed a comprehensive meta-analysis of published studies to clarify the impact of plasma ESR1 mutations on clinical outcomes for patients after subsequent ET. Materials and methods: An electronic search was performed to identify eligible studies. Studies analyzing progression-free survival (PFS) and/or overall survival (OS) according to plasma ESR1 mutation status after subsequent ET were included...
2018: OncoTargets and Therapy
Mary Ellen Molloy, Monika Lewinska, Amanda K Williamson, Thanh Thao Nguyen, Gamze Kuser-Abali, Lu Gong, Jiawei Yan, John B Little, Pier Paolo Pandolfi, Zhi-Min Yuan
ZBTB7A, a member of the POZ/BTB and Krüppel (POK) family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha (ERα)-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ERα-positive. ERα carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ERα expression in ERα-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ERα...
August 1, 2018: Journal of Molecular Cell Biology
Jamie R Kutasovic, Amy E McCart Reed, Renique Males, Sarah Sim, Jodi M Saunus, Andrew Dalley, Christopher McEvoy, Liana Dedina, Gregory Miller, Stephen Peyton, Lynne Reid, Samir Lal, Colleen Niland, Kaltin Ferguson, Andrew Fellowes, Fares Al-Ejeh, Sunil R Lakhani, Margaret C Cummings, Peter T Simpson
Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathologic and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy number profiling and targeted sequencing of 386 cancer-related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46...
September 24, 2018: Journal of Pathology. Clinical Research
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
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