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HER2 amplification

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https://www.readbyqxmd.com/read/28327938/targeting-the-fibroblast-growth-factor-receptor-2-in-gastric-cancer-promise-or-pitfall
#1
C Hierro, M Alsina, M Sánchez, V Serra, J Rodon, J Tabernero
Gastric cancer is the third leading cause of death from cancer worldwide. Systemic chemotherapy remains the mainstay therapeutic option for this poor prognosis cancer. Trastuzumab, the epidermal growth factor receptor 2 (ERBB2 or HER2)-antibody, is the only biological agent approved for the molecularly-selected population of HER2-positive gastric cancer patients. Over the last decade, several groups have been working for deepening into the molecular characterization of gastric cancer, shedding some light into the heterogeneity of this tumour...
March 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327926/genomic-characterisation-of-her2-positive-breast-cancer-and-response-to-neoadjuvant-trastuzumab-and-chemotherapy-results-from-the-acosog-z1041-alliance-trial
#2
R Lesurf, O L Griffith, M Griffith, J Hundal, L Trani, M A Watson, R Aft, M J Ellis, D Ota, V J Suman, F Meric-Bernstam, A M Leitch, J C Boughey, G Unzeitig, A U Buzdar, K K Hunt, E R Mardis
Background: HER2 ( ERBB2 ) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference [1]. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483)...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28294295/breast-cancer-major-changes-in-the-american-joint-committee-on-cancer-eighth-edition-cancer-staging-manual
#3
Armando E Giuliano, James L Connolly, Stephen B Edge, Elizabeth A Mittendorf, Hope S Rugo, Lawrence J Solin, Donald L Weaver, David J Winchester, Gabriel N Hortobagyi
Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system...
March 14, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28292264/establishment-of-patient-derived-gastric-cancer-xenografts-a-useful-tool-for-preclinical-evaluation-of-targeted-therapies-involving-alterations-in-her-2-met-and-fgfr2-signaling-pathways
#4
Haiyong Wang, Jun Lu, Jian Tang, Shitu Chen, Kuifeng He, Xiaoxia Jiang, Weiqin Jiang, Lisong Teng
BACKGROUND: Targeted therapies are emerging treatment options for gastric cancer (GC). Patient-derived tumor xenograft(PDX) models of GC closely retain the features of the original clinical cancer, offering a powerful tool for preclinical drug efficacy testing. This study aimed to establish PDX GC models, and explore therapeutics targeting Her2, MET(cMet), and FGFR2, which may assist doctor to select the proper target therapy for selected patients. METHODS: GC tissues from 32 patients were collected and implanted into immuno-deficient mice...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28277540/p53-loss-of-heterozygosity-is-a-necessary-prerequisite-for-mutant-p53-stabilization-and-gain-of-function-in-vivo
#5
Evguenia M Alexandrova, Safia A Mirza, Sulan Xu, Ramona Schulz-Heddergott, Natalia D Marchenko, Ute M Moll
Missense mutations in TP53 comprise >75% of all p53 alterations in cancer, resulting in highly stabilized mutant p53 proteins that not only lose their tumor-suppressor activity, but often acquire oncogenic gain-of-functions (GOFs). GOF manifests itself in accelerated tumor onset, increased metastasis, increased drug resistance and shortened survival in patients and mice. A known prerequisite for GOF is mutant p53 protein stabilization, which itself is linked to aberrant protein conformation. However, additional determinants for mutant p53 stabilization likely exist...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28267250/counting-invasive-breast-cancer-cells-in-her2-silver-in-situ-hybridization-test-how-many-cells-are-enough
#6
António Polónia, Catarina Eloy, João Pinto, Ana Costa Braga, Guilherme Oliveira, Fernando Schmitt
AIM: Evaluate the intra and interobserver reproducibility of the HER2 ISH test in breast cancer measuring the impact of counting different numbers of invasive cancer cells. MATERIALS AND METHODS: A cohort of 101 primary invasive breast cancer cases were evaluated for HER2 gene amplification by SISH and the concordance among 4 observers with different levels of experience was determined counting different numbers of invasive cancer cells. The evaluation of the samples included scoring 20 nuclei, in three different areas...
March 7, 2017: Histopathology
https://www.readbyqxmd.com/read/28239564/cancer-stem-cells-and-early-stage-basal-like-breast-cancer
#7
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment...
May 10, 2016: World Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28235632/utility-of-comprehensive-genomic-sequencing-for-detecting-her2-positive-colorectal-cancer
#8
Yoshifumi Shimada, Ryoma Yagi, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Yo Sato, Takeaki Matsuzawa, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Takashi Kawasaki, Kei-Ichi Homma, Hiroshi Izutsu, Keisuke Kodama, Jennifer E Ring, Alexei Protopopov, Stephen Lyle, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai
HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC...
February 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28228710/her2-positive-neuroendocrine-breast-cancer-case-report-and-review-of-literature
#9
Arpine Gevorgyan, Giacomo Bregni, Giulia Galli, Elisa Zanardi, Filippo de Braud, Serena Di Cosimo
BACKGROUND: Neuroendocrine carcinoma is an uncommon histology for breast cancer. CASE REPORT: Our patient underwent right quadrantectomy for a neuroendocrine carcinoma in 1984 and had a bone relapse 30 years later. After thorough pathological and immunohistochemical analysis the diagnosis was confirmed and HER2 amplification was observed. Here we discuss the management, rationale and results of HER2-targeted therapy in advanced neuroendocrine breast carcinoma.
December 2016: Breast Care
https://www.readbyqxmd.com/read/28223103/her2-amplification-and-cetuximab-efficacy-in-patients-with-metastatic-colorectal-cancer-harboring-wild-type-ras-and-braf
#10
Jae Ho Jeong, Jihun Kim, Yong Sang Hong, Dalyong Kim, Jeong Eun Kim, Sun Young Kim, Kyu-Pyo Kim, Young-Kwang Yoon, Deokhoon Kim, Sung-Min Chun, Yangsoon Park, Se Jin Jang, Tae Won Kim
BACKGROUND: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type RAS. Human epidermal growth factor receptor 2 (HER2) amplification may be a mechanism of cetuximab resistance. We evaluated the association between HER2 amplification and cetuximab efficacy in patients with mCRC harboring wild-type RAS and BRAF. PATIENTS AND METHODS: Between December 2003 and June 2013, we identified 142 patients with mCRC whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF using high throughput sequencing (OncoMap version 4...
January 25, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28219246/dna-generated-electric-current-biosensor
#11
Lanshuang Hu, Shengqiang Hu, Linyan Guo, Congcong Shen, Minghui Yang, Avraham Rasooly
In addition to its primary function as a genetic material, deoxyribonucleic acid (DNA) is also a potential biologic energy source for molecular electronics. For the first time, we demonstrate that DNA can generate a redox electric current. As an example of this new functionality, DNA generated redox current was used for electrochemical detection of human epidermal growth factor receptor 2 (HER2), a clinically important breast cancer biomarker. To induce redox current, the phosphate of the single stranded DNA aptamer backbone was reacted with molybdate to form redox molybdophosphate precipitate and generate an electrochemical current of ∼16...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28219002/molecular-testing-for-gastrointestinal-cancer
#12
REVIEW
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28216025/pi3k-akt-mtor-inhibitors-in-breast-cancers-from-tumor-cell-signaling-to-clinical-trials
#13
REVIEW
Dey Nandini, De Pradip, Leyland-Jones Brian
Breast cancer (BC) is the most common women cancer and second most common cause of cancer death in women. A woman living in the United States has 12.3% lifetime risk of being diagnosed with BC. From the genomics point of view, the most common three subtypes of BC encountered in clinics are HR+, HER2+, and TNBC or basal-like BC. Estrogen receptor (ER) status or HER2 amplification or chemotherapy is not sufficient to understand the underlying mechanisms of disease progression and resistance (de novo or acquire)...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28211519/palindromic-amplification-of-the-erbb2-oncogene-in-primary-her2-positive-breast-tumors
#14
Michael Marotta, Taku Onodera, Jeffrey Johnson, G Thomas Budd, Takaaki Watanabe, Xiaojiang Cui, Armando E Giuliano, Atsushi Niida, Hisashi Tanaka
Oncogene amplification confers a growth advantage to tumor cells for clonal expansion. There are several, recurrently amplified oncogenes throughout the human genome. However, it remains unclear whether this recurrent amplification is solely a manifestation of increased fitness resulting from random amplification mechanisms, or if a genomic locus-specific amplification mechanism plays a role. Here we show that the ERBB2 oncogene at 17q12 is susceptible to palindromic gene amplification, a mechanism characterized by the inverted (palindromic) duplication of genomic segments, in HER2-positive breast tumors...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#15
Darien E Reed, Kevan M Shokat
Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28196634/objective-domain-specific-her2-measurement-in-uterine-and-ovarian-serous-carcinomas-and-its-clinical-significance
#16
Daniel E Carvajal-Hausdorf, Kurt A Schalper, Yalai Bai, Jonathan Black, Alessandro D Santin, David L Rimm
INTRODUCTION: HER2 overexpression/amplification is identified in up to 40% of uterine serous carcinomas (USC) and 10% of ovarian serous carcinomas (OSC). However, clinical trials using various HER2-targeted agents failed to show significant responses. FDA-approved HER2 assays target only the protein's intracellular domain (ICD) and not the extracellular domain (ECD). Previous quantitative studies in breast cancer by our group have shown that ICD of HER2 is expressed in some cases that do not express the HER2 ECD...
February 11, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28192599/impact-of-an-alternative-chromosome-17-probe-and-the-2013-american-society-of-clinical-oncology-and-college-of-american-pathologists-guidelines-on-fluorescence-in-situ-hybridization-for-the-determination-of-her2-gene-amplification-in-breast-cancer
#17
Alana R Donaldson, Shashirekha Shetty, Zhen Wang, Christine L Rivera, Bryce P Portier, G Thomas Budd, Erinn Downs-Kelly, Christopher P Lanigan, Benjamin C Calhoun
BACKGROUND: The dual-probe fluorescence in situ hybridization (FISH) assay for human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provides an HER2:CEP17 (centromere enumeration probe for chromosome 17) ratio. Copy number alteration (CNA) in CEP17 may skew this ratio. The authors analyzed the impact of the 2013 American Society of Oncology/College of American Pathologists (ASCO/CAP) guidelines and an alternative chromosome 17 probe on HER2 status in tumor specimens with CEP17 CNA...
February 13, 2017: Cancer
https://www.readbyqxmd.com/read/28183331/phase-ii-randomized-placebo-controlled-study-of-dovitinib-in-combination-with-fulvestrant-in-postmenopausal-patients-with-hr-her2-breast-cancer-that-had-progressed-during-or-after-prior-endocrine-therapy
#18
Antonino Musolino, Mario Campone, Patrick Neven, Neelima Denduluri, Carlos H Barrios, Javier Cortes, Kimberly Blackwell, Hatem Soliman, Zsuzsanna Kahan, Hervé Bonnefoi, Matthew Squires, Yong Zhang, Stephanie Deudon, Michael M Shi, Fabrice André
BACKGROUND: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor-positive (HR(+)), human epidermal growth factor receptor 2-negative (HER2(-)) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer. METHODS: In this randomized, placebo-controlled phase II trial, we evaluated whether the addition of dovitinib to fulvestrant would improve outcomes in postmenopausal patients with HR(+), HER2(-) advanced breast cancer that had progressed during or after prior ET...
February 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#19
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177558/tmem16a-ano1-suppression-improves-response-to-antibody-mediated-targeted-therapy-of-egfr-and-her2-erbb2
#20
Sucheta Kulkarni, Anke Bill, Neal R Godse, Nayel I Khan, Jason I Kass, Kevin Steehler, Carolyn Kemp, Kara Davis, Carol A Bertrand, Avani R Vyas, Douglas E Holt, Jennifer R Grandis, L Alex Gaither, Umamaheswar Duvvuri
TMEM16A, a Ca(2+) -activated Cl(-) channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl(-) channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl(-) channel inhibition...
February 8, 2017: Genes, Chromosomes & Cancer
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