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HER2 amplification

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https://www.readbyqxmd.com/read/27932758/-expressions-of-her2-and-topo-ii%C3%AE-in-breast-cancer-and-%C3%A2-its-clinical-significance
#1
Ping Shuai
To detect the expressions of human epidermal growth factor receptor 2 (HER2) and Topo IIα in breast cancer, and to analyze the clinical significance of neoadjuvant chemotherapy for the anthracycline-based drugs.
 Methods: The HER2 and Topo IIα gene and protein expressions in cancer tissues from 189 patients with breast cancer were detected by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). And the objective response rate (ORR) and pathological complete rate (pCR) were analyzed...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27931045/breast-cancer-in-neurofibromatosis-type-1-overrepresentation-of-unfavourable-prognostic-factors
#2
Elina Uusitalo, Roope A Kallionpää, Samu Kurki, Matti Rantanen, Janne Pitkäniemi, Pauliina Kronqvist, Pirkko Härkönen, Riikka Huovinen, Olli Carpen, Minna Pöyhönen, Sirkku Peltonen, Juha Peltonen
BACKGROUND: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. METHODS: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls...
December 8, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#3
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#4
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#5
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#6
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27904779/generation-characterization-and-maintenance-of-trastuzumab-resistant-her2-breast-cancer-cell-lines
#7
Sandra Zazo, Paula González-Alonso, Ester Martín-Aparicio, Cristina Chamizo, Ion Cristóbal, Oriol Arpí, Ana Rovira, Joan Albanell, Pilar Eroles, Ana Lluch, Juan Madoz-Gúrpide, Federico Rojo
Trastuzumab became the therapy of choice for patients with HER2-positive breast cancer in 1998, and it has provided clinical benefit ever since. However, a significant percentage of patients show primary resistance to trastuzumab at diagnosis, and most patients with metastatic disease that initially respond to trastuzumab eventually progress (acquired resistance). Consequently, there is an urgent need to improve our knowledge of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904700/detection-of-gene-copy-number-alterations-in-dcis-and-invasive-breast-cancer-by-qm-fish
#8
Aifeng Pan, Yawei Zhou, Kun Mu, Yansong Liu, Feifei Sun, Peng Li, Li Li
The exact roles of copy number alteration (CNA) in initiation, progression and immunotherapy of breast cancer and the genomic alterations behind progression from ductal carcinoma in situ (DCIS) to invasive carcinoma remain unknown. Quantitative multi-gene fluorescence in situ hybridization (QM-FISH) opens a possibility of large scale genomic analysis of specific deletions and amplifications with high-resolution at one cell level. We detected CNAs of 30 genes using QM-FISH and analyzed their association with clinicopathological parameters and patients' outcomes in 66 breast cancers with synchronous invasive carcinoma and DCIS...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903463/her2-transmembrane-mutations-v659-g660-that-stabilize-homo-and-hetero-dimerization-are-rare-oncogenic-drivers-in-lung-adenocarcinoma-that-respond-to-afatinib
#9
Sai-Hong Ignatius Ou, Alexa B Schrock, Eduard V Bocharov, Samuel J Klempner, Carolina Kawamura Haddad, Gary Steinecker, Melissa Johnson, Barbara J Gitlitz, Jon Chung, Paulo V Campregher, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, James H Suh, Siraj M Ali, Vamsidhar Velcheti
INTRODUCTION: HER2 transmembrane domain (TMD) mutations (HER2(V659E), HER2(G660D)) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown. METHODS: We prospectively analyzed 8,551 consecutive lung adenocarcinomas using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions. RESULTS: We identified 15 cases (0...
November 26, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27900589/intrinsic-her2-v777l-mutation-mediates-resistance-to-trastuzumab-in-a-breast-cancer-patient
#10
Yosuke Hirotsu, Hiroshi Nakagomi, Kenji Amemiya, Toshio Oyama, Masayuki Inoue, Hitoshi Mochizuki, Masao Omata
HER2 (ERBB2) is an oncogene and 20% of breast cancers display HER2 amplification. The HER2 monoclonal antibody, trastuzumab, is used to treat breast cancers that display HER2 amplification, with good responses in 80-90% of cases; however, 10% of tumours develop resistance to trastuzumab. In this study, we collected data of primary breast cancer patients who treated at hospital during 2004-2014. In our cohort, 205 of 1497 primary breast cancer patients showed HER2-amplification, and 20 experienced recurrence after trastuzumab therapy...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27899970/fish-testing-of-her2-immunohistochemistry-1-invasive-breast-cancer-with-unfavorable-characteristics
#11
Stella Petroni, Lucia Caldarola, Rachele Scamarcio, Francesco Giotta, Agnese Latorre, Anita Mangia, Giovanni Simone
Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895501/a-fish-based-method-for-assessment-of-her-2-amplification-status-in-breast-cancer-circulating-tumor-cells-following-cellsearch-isolation
#12
Henrik Frithiof, Kristina Aaltonen, Lisa Rydén
INTRODUCTION: Amplification of the HER-2/neu (HER-2) proto-oncogene occurs in 10%-15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting growth of cancer cells. Tumor classification is determined in primary tumor tissue and metastatic biopsies. However, malignant cells tend to alter their phenotype during disease progression. Circulating tumor cell (CTC) analysis may serve as an alternative to repeated biopsies. The Food and Drug Administration-approved CellSearch system allows determination of the HER-2 protein, but not of the HER-2 gene...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27885439/weekly-paclitaxel-plus-carboplatin-with-or-without-trastuzumab-as-neoadjuvant-chemotherapy-for-her2-positive-breast-cancer-loss-of-her2-amplification-and-its-impact-on-response-and-prognosis
#13
Ruo-Xi Wang, Sheng Chen, Xi Jin, Can-Ming Chen, Zhi-Ming Shao
PURPOSE: Neoadjuvant chemotherapy (NCT) plus anti-HER2 agents are the standard of care for locally advanced HER2-positive breast cancer. The aim of this study was to evaluate the prevalence and prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without trastuzumab. METHODS: 549 consecutive HER2-positive patients were included in this study. 379 patients were treated with paclitaxel, carboplatin, and trastuzumab (PCH cohort) and 170 were treated with paclitaxel and carboplatin only (PC cohort)...
November 24, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27866824/detection-of-her2-overexpressing-cancer-cells-using-keyhole-shaped-chamber-array-employing-a-magnetic-droplet-handling-system
#14
Mina Okochi, Shinji Koike, Masayoshi Tanaka, Hiroyuki Honda
An on-chip gene expression analysis compartmentalized in droplets was developed for detection of cancer cells at a single-cell level. The chip consists of a keyhole-shaped reaction chamber with hydrophobic modification employing a magnetic bead-droplet-handling system with a gate for bead separation. Using three kinds of water-based droplets in oil, a droplet with sample cells, a lysis buffer with magnetic beads, and RT-PCR buffer, parallel magnetic manipulation and fusion of droplets were performed using a magnet-handling device containing small external magnet patterns in an array...
November 11, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27863726/-met-receptor-inhibition-hope-against-resistance-to-targeted-therapies
#15
REVIEW
Audrey Hochart, Pierre Leblond, Xuefen Le Bourhis, Samuel Meignan, David Tulasne
Overcoming the drug resistance remains a crucial issue in cancer treatment. For refractory patients, the use of MET receptor tyrosine kinase inhibitors seems to be hopeful. Indeed, important mechanisms underlying drug resistance argue for association of MET inhibitors with targeted therapies, both on first-line to prevent a primary resistance and on the second line to overcoming acquired resistance. Indeed, met gene amplification is the second most common alteration involved in acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies in non-small cells lung cancer (NSCLC)...
November 15, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27837339/her2-mrna-transcript-quantitation-in-breast-cancer
#16
K Meehan, B Clynick, B Mirzai, P Maslen, J M Harvey, W N Erber
PURPOSE: The human epidermal growth factor receptor 2 (HER2) status in breast cancer is important for prognostic prediction and the determination of optimal treatment. Current methods rely on protein expression, as determined by immunohistochemistry (IHC), as well as gene amplification as determined by in situ hybridisation (ISH). We explored whether quantitative droplet digital PCR (ddPCR) can be used for the detection and absolute quantitation of HER2 mRNA. METHODS: Digital droplet PCR (ddPCR) was performed for HER2 mRNA on 178 formalin-fixed paraffin-embedded (FFPE) breast cancer specimens...
November 11, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27835607/p16-overexpression-and-9p21-deletion-are-linked-to-unfavorable-tumor-phenotype-in-breast-cancer
#17
Patrick Lebok, Magdalena Roming, Martina Kluth, Christina Koop, Cansu Özden, Berivan Taskin, Khakan Hussein, Annette Lebeau, Isabell Witzel, Linn Wölber, Stefan Geist, Peter Paluchowski, Christian Wilke, Uwe Heilenkötter, Volkmar Müller, Barbara Schmalfeldt, Ronald Simon, Guido Sauter, Luigi Terracciano, Rainer Horst Krech, Albert von der Assen, Eike Burandt
Overexpression of the p16 tumor suppressor, but also deletion of its gene locus 9p21, is linked to unfavorable tumor phenotype and poor prognosis in breast cancer. To better understand these contradictory observations, and to clarify the prognostic impact of p16 expression and 9p21 deletion, a tissue microarray (TMA) with 2,197 breast cancers was analyzed by fluorescence in-situ hybridization and immunohistochemistry (FISH) for 9p21 deletion and p16 expression. p16 immunostaining was weak in 25.6%, moderate in 7...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825109/her2-mutations-in-chinese-patients-with-non-small-cell-lung-cancer
#18
Zhengbo Song, Xinmin Yu, Zhiyong Shi, Jun Zhao, Yiping Zhang
BACKGROUND: ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear. PATIENTS AND METHODS: Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27823638/molecular-characteristics-of-biliary-tract-cancer
#19
REVIEW
Davendra P S Sohal, Shiva Shrotriya, Mohamed Abazeed, Michael Cruise, Alok Khorana
Biliary tract cancers (intrahepatic, perihilar and extrahepatic cholangiocarcinoma, and gallbladder and cystic duct cancers) are uncommon but highly lethal malignancies. Clinical presentation is often late, precluding curative surgical resection in most cases. For advanced disease, therapeutic options are limited to systemic chemotherapy, with suboptimal outcomes. An understanding of the molecular characteristics of biliary tract cancers may allow the clinical development of therapies targeting actionable alterations with the ultimate goal of improving clinical outcomes...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27815036/crispr-mediated-targeting-of-her2-inhibits-cell-proliferation-through-a-dominant-negative-mutation
#20
Huajing Wang, William Sun
With the discovery of the CRISPR/Cas9 technology, genome editing could be performed in a rapid, precise and effective manner. Its potential applications in functional interrogation of cancer-causing genes and cancer therapy have been extensively explored. In this study, we demonstrated the use of the CRISPR/Cas9 system to directly target the oncogene HER2. Directing Cas9 to exons of the HER2 gene inhibited cell growth in breast cancer cell lines that harbor amplification of the HER2 locus. The inhibitory effect was potentiated with the addition of PARP inhibitors...
January 28, 2017: Cancer Letters
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