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HER2 amplification

L Fahmi, H Fettachi, H Hamdaoui, H Mossafa
No abstract text is available yet for this article.
March 2018: European Journal of Cancer
Hidejiro Torigoe, Kazuhiko Shien, Tatsuaki Takeda, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Masakiyo Sakaguchi, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors...
March 13, 2018: Cancer Science
Andreas H Scheel, Frédérique Penault-Llorca, Wedad Hanna, Gustavo Baretton, Peter Middel, Judith Burchhardt, Manfred Hofmann, Bharat Jasani, Josef Rüschoff
BACKGROUND: Detection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas. Immunohistochemistry (IHC) of the HER2 protein is the most common screening test, thus precise and reproducible IHC-scoring is of utmost importance. Interobserver variance still is a problem; in particular in gastric carcinomas the reliable differentiation of IHC scores 2+ and 1+ is challenging. Herein we describe the physical basis of what we called the 'magnification rule': Different microscope objectives are employed to reproducibly subdivide the continuous spectrum of IHC staining intensities into distinct categories (1+, 2+, 3+)...
March 12, 2018: Diagnostic Pathology
Tammey J Naab, Anita Gautam, Luisel Ricks-Santi, Ashwini K Esnakula, Yasmine M Kanaan, Robert L DeWitty, Girmay Asgedom, Khepher H Makambi, Massih Abawi, Jan K Blancato
BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification...
March 9, 2018: BMC Cancer
Lionel Kankeu Fonkoua, Nelson S Yee
Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively...
March 9, 2018: Biomedicines
Luc Cabel, Alina Fuerea, Ludovic Lacroix, Capucine Baldini, Patricia Martin, Antoine Hollebecque, Sophie Postel-Vinay, Andrea Varga, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Jean Yves Scoazec, Samy Ammari, Fabrice André, Jean-Charles Soria, Christophe Massard, Loic Verlingue
A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2- altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification...
February 9, 2018: Oncotarget
Yoshimasa Miyagawa, Yosuke Matsushita, Hiromu Suzuki, Masato Komatsu, Tetsuro Yoshimaru, Ryuichiro Kimura, Ayako Yanai, Junko Honda, Akira Tangoku, Mitsunori Sasa, Yasuo Miyoshi, Toyomasa Katagiri
Triple-negative breast cancer (TNBC), defined as breast cancer lacking estrogen- and progesterone‑receptor expression and human epidermal growth factor receptor 2 (HER2) amplification, is a heterogeneous disease. RNA-sequencing analysis of 15 TNBC specimens and The Cancer Genome Atlas-TNBC dataset analysis identified the frequent downregulation of leucine-rich repeat-containing 26 (LRRC26), which negatively regulates nuclear factor-κB (NF-κB) signaling, in TNBC tissues. Quantitative polymerase chain reaction and bisulfite pyrosequencing analyses revealed that LRRC26 was frequently silenced in TNBC tissues and cell lines as a result of promoter methylation...
March 5, 2018: International Journal of Oncology
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
Abdelbaset Buhmeida, Mourad Assidi, Jaudah Al-Maghrabi, Ashraf Dallol, Abdulrahman Sibiany, Mahmoud Al-Ahwal, Adeel Chaudhary, Adel Abuzenadah, Mohammed Al-Qahtani
BACKGROUND: Human epidermal growth factor recptor-2 (HER2) was identified as a driver gene in several types of cancers with both prognostic and predictive value. However, the molecular association of HER2 gene mutation with HER2 gene amplification and/or protein expression in cancer tissues has not been clearly defined. Moreover, there is little information available on HER2 status role in tumor progression and metastasis in colorectal carcinoma (CRC) compared to other solid tumors. The aim of this study was to evaluate both HER2 amplification and protein expression profiles using immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) techniques, respectively...
March 5, 2018: Cancer Investigation
Ziping Wu, Shuguang Xu, Liheng Zhou, Wenjin Yin, Yanpin Lin, Yueyao Du, Yaohui Wang, Yiwei Jiang, Kai Yin, Jie Zhang, Jinsong Lu
Background: The aims of this study were to determine whether the quantitative HER2 gene amplification level is related to the key clinicopathological features that represent the aggressiveness of breast cancer (BC) and to determine whether the quantitative HER2 gene amplification level could predict the treatment response in the subset of HER2-positive patients who received neoadjuvant targeted therapy. Materials and methods: Patients treated with weekly cisplatin- and paclitaxel-based neoadjuvant chemotherapy, who had undergone both immunohistochemistry and the fluorescence in situ hybridization test for HER2 , were included in the study (n=103)...
2018: OncoTargets and Therapy
Joris P Bulte, Altuna Halilovic, Shona Kalkman, Patricia H J van Cleef, Paul J van Diest, Luc J A Strobbe, Johannes H W de Wilt, Peter Bult
AIMS: To establish whether core needle biopsy (CNB) specimens processed with an accelerated processing method with short fixation time can be used to accurately determine HER2 status of breast cancer. METHODS AND RESULTS: A consecutive case series from two high volume breast clinics was created. We compared routine HER2 immunohistochemistry (IHC) assessment between accelerated processing CNB specimens and routinely processed postoperative excision specimens. Additional amplification-based testing was performed in cases with equivocal results...
March 1, 2018: Histopathology
Sadakatsu Ikeda, Igor F Tsigelny, Åge A Skjevik, Yuko Kono, Michel Mendler, Alexander Kuo, Jason K Sicklick, Gregory Heestand, Kimberly C Banks, AmirAli Talasaz, Richard B Lanman, Scott Lippman, Razelle Kurzrock
BACKGROUND: Because imaging has a high sensitivity to diagnose hepatocellular carcinoma (HCC) and tissue biopsies carry risks such as bleeding, the latter are often not performed in HCC. Blood-derived circulating tumor DNA (ctDNA) analysis can identify somatic alterations, but its utility has not been characterized in HCC. MATERIALS AND METHODS: We evaluated 14 patients with advanced HCC (digital ctDNA sequencing [68 genes]). Mutant relative to wild-type allele fraction was calculated...
February 27, 2018: Oncologist
Wen-Ling Kuo, Shir-Hwa Ueng, Chun-Hsing Wu, Li-Yu Lee, Yun-Shien Lee, Ming-Chin Yu, Shin-Cheh Chen, Chi-Chang Yu, Chi-Neu Tsai
The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements...
February 26, 2018: Human Cell
Konstantinos V Floros, Timothy L Lochmann, Bin Hu, Carles Monterrubio, Mark T Hughes, Jason D Wells, Cristina Bernadó Morales, Maninderjit S Ghotra, Carlotta Costa, Andrew J Souers, Sosipatros A Boikos, Joel D Leverson, Ming Tan, Violeta Serra, Jennifer E Koblinski, Joaquin Arribas, Aleix Prat, Laia Paré, Todd W Miller, Mikhail G Dozmorov, Hisashi Harada, Brad E Windle, Maurizio Scaltriti, Anthony C Faber
HER2 ( ERBB2 ) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR -mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment...
February 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Toru Kumagai, Yasuhiko Tomita, Shin-Ichi Nakatsuka, Madoka Kimura, Kei Kunimasa, Takako Inoue, Motohiro Tamiya, Kazumi Nishino, Yoshiyuki Susaki, Takashi Kusu, Toshiteru Tokunaga, Jiro Okami, Masahiko Higashiyama, Fumio Imamura
BACKGROUND: Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. METHODS: HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively...
February 23, 2018: Thoracic Cancer
Vladimir M Moiseyenko, Fedor V Moiseyenko, Grigoriy A Yanus, Ekatherina Sh Kuligina, Anna P Sokolenko, Ilya V Bizin, Alexey A Kudriavtsev, Svetlana N Aleksakhina, Nikita M Volkov, Vyacheslav A Chubenko, Kseniya S Kozyreva, Mikhail M Kramchaninov, Alexandr S Zhuravlev, Kseniya V Shelekhova, Denis V Pashkov, Alexandr O Ivantsov, Aigul R Venina, Tatyana N Sokolova, Elena V Preobrazhenskaya, Natalia V Mitiushkina, Alexandr V Togo, Aglaya G Iyevleva, Evgeny N Imyanitov
BACKGROUND: Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests...
February 22, 2018: Clinical Drug Investigation
Julie Johnson, Darrell C Bessette, Jodi M Saunus, Chanel E Smart, Sarah Song, Rebecca L Johnston, Sibylle Cocciardi, Esdy N Rozali, Cameron N Johnstone, Ana Christina Vargas, Stephen H Kazakoff, Victorian Cancer BioBank, Kum Kum Khanna, Sunil R Lakhani, Georgia Chenevix-Trench, Peter T Simpson, Katia Nones, Nicola Waddell, Fares Al-Ejeh
PURPOSE: We aimed to generate and characterize a novel cell line from a breast cancer bone metastasis to better study the progression of the disease. METHODS: The cell line, P7731, was derived from a metastatic bone lesion of a breast cancer patient and assessed for marker expression. P7731 was analyzed for DNA copy number variation, somatic mutations, and gene expression and was compared with the primary tumor. RESULTS: P7731 cells are negative for estrogen receptor alpha (ERα), progesterone receptor (PR), and HER2 (triple-negative); strongly express vimentin (100% of cells positive) and also express cytokeratins 8/18 and 19 but at lower frequencies...
February 21, 2018: Breast Cancer Research and Treatment
Anissa Moktefi, Damien Pouessel, Jing Liu, Nanor Sirab, Pascale Maille, Pascale Soyeux, Christiane Copie Bergman, Marie Luce Auriault, Dimitri Vordos, Alexandre de la Taille, Stéphane Culine, Yves Allory
Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder...
February 21, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Takahiro Yoshioka, Kazuhiko Shien, Kei Namba, Hidejiro Torigoe, Hiroki Sato, Shuta Tomida, Hiromasa Yamamoto, Hiroaki Asano, Junichi Soh, Kazunori Tsukuda, Takeshi Nagasaka, Toshiyoshi Fujiwara, Shinichi Toyooka
Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-HER2 drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. At first, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs...
February 21, 2018: Cancer Science
Zhenfang Du, Christine M Lovly
Receptor tyrosine kinases (RTKs) play an important role in a variety of cellular processes including growth, motility, differentiation, and metabolism. As such, dysregulation of RTK signaling leads to an assortment of human diseases, most notably, cancers. Recent large-scale genomic studies have revealed the presence of various alterations in the genes encoding RTKs such as EGFR, HER2/ErbB2, and MET, amongst many others. Abnormal RTK activation in human cancers is mediated by four principal mechanisms: gain-of-function mutations, genomic amplification, chromosomal rearrangements, and / or autocrine activation...
February 19, 2018: Molecular Cancer
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