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Her2 breast cancer

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https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#1
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935425/how-is-herstatin-a-tumour-suppressor-splice-variant-of-the-oncogene-her2-regulated
#2
Marco Silipo, Hannah Gautrey, Swapna Satam, Thomas Lennard, Alison Tyson-Capper
The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is over-expressed in 20-30% of breast tumours leading to faster growing and more aggressive tumours. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumour suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin...
December 9, 2016: RNA Biology
https://www.readbyqxmd.com/read/27932758/-expressions-of-her2-and-topo-ii%C3%AE-in-breast-cancer-and-%C3%A2-its-clinical-significance
#3
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/27932757/-expressions-of-epithelial-cell-adhesion-molecule-vimentin-and-n-cadherin-in-molecular-subtypes-of-breast-cancer-and-the-correlation-among-them
#4
Limei Fu, Min Liu, Xuemei Yu, Xinjun Li
To examine the expressions of epithelial cell adhesion molecule (EpCAM), vimentin and N-cadherin in breast cancer and its molecular subtypes, and to explore the correlation among them.
 Methods: The expressions of EpCAM, vimentin and N-cadherin were detected by immunohistochemistry in 835 patients with breast cancer, and their correlations with clinical pathological features and prognosis were analyzed.
 Results: The expression rates of EpCAM, vimentin and N-cadherin in the patients were 53.4%, 11.4% and 9...
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
#5
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/27928473/pathological-characteristics-of-triple-negative-breast-cancer-at-main-referral-teaching-hospital-april-2014-to-april-2015-tehran-iran
#6
Alireza Abdollahi, Mehrnoosh Etemadi
Background: Triple-negative breast cancers (TNBC) are defined as breast cancers with lack of estrogen and progesterone receptors and no overexpression of human epidermal growth factor receptor 2 (HER2). This study was performed to determine the frequency and pathologic features of TNBC in Iranian patients. Subjects and Methods: This cross-sectional study was performed on patients with breast cancer who referred to Cancer Institute, affiliated to Tehran University of Medical Sciences, from April 2014 to April 2015...
October 1, 2016: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/27927046/advances-in-chemical-pharmacotherapy-to-manage-advanced-breast-cancer
#7
Andrea Gombos, Ahmad Awada
Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life. Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents...
December 7, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#8
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/27926493/developmental-therapeutics-for-inflammatory-breast-cancer-biology-and-translational-directions
#9
REVIEW
Ricardo Costa, Cesar A Santa-Maria, Giovanna Rossi, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Francis J Giles, Massimo Cristofanilli
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, which accounts for approximately 3% of cases of breast malignancies. Diagnosis relies largely on its clinical presentation, and despite a characteristic phenotype, underlying molecular mechanisms are poorly understood. Unique clinical presentation indicates that IBC is a distinct clinical and biological entity when compared to non-IBC. Biological understanding of non-IBC has been extrapolated into IBC and targeted therapies for HER2 positive (HER2+) and hormonal receptor positive non-IBC led to improved patient outcomes in the recent years...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#10
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair...
December 7, 2016: Journal of Pathology
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
#11
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/27923036/cotargeting-of-cyp-19-aromatase-and-emerging-pivotal-signalling-pathways-in-metastatic-breast-cancer
#12
REVIEW
Stine Daldorff, Randi Margit Ruud Mathiesen, Olav Erich Yri, Hilde Presterud Ødegård, Jürgen Geisler
Aromatase inhibition is one of the cornerstones of modern endocrine therapy of oestrogen receptor-positive (ER+) metastatic breast cancer (MBC). The nonsteroidal aromatase inhibitors anastrozole and letrozole, as well as the steroidal aromatase inactivator exemestane, are the preferred drugs and established worldwide in all clinical phases of the disease. However, although many patients suffering from MBC experience an initial stabilisation of their metastatic burden, drug resistance and disease progression occur frequently, following in general only a few months on treatment...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27920729/transcriptional-network-architecture-of-breast-cancer-molecular-subtypes
#13
Guillermo de Anda-Jáuregui, Tadeo E Velázquez-Caldelas, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27920688/complete-and-sustained-response-with-a-doublet-chemotherapy-protocol-in-an-81-year-old-patient-with-metastatic-breast-cancer
#14
Taynah Cascaes Puty, Gabriel S A Brito, Mariana S Dias, Henrique C Miranda, Juliana R Chaves, Heryvelton L Freitas, Luís E W Carvalho
Metastatic breast cancer (MBC) entails an overall 5-year survival of approximately 25%. The choice of therapy is influenced by expression of the HER2 gene and hormone receptors, by a disease-free interval, and by age. The use of paclitaxel combined with gemcitabine (doublet protocol) has shown efficacy as first-line treatment for MBC in either initial or maintenance therapy when compared to monotherapy with paclitaxel. There is evidence showing that the doublet protocol is a good alternative to maintenance therapy in women under 50 years old...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920624/neoadjuvant-chemotherapy-with-docetaxel-carboplatin-and-weekly-trastuzumab-is-active-in-her2-positive-early-breast-cancer-results-after-a-median-follow-up-of-over-4-years
#15
Hans-Christian Kolberg, Leyla Akpolat-Basci, Miltiades Stephanou, Bahriye Aktas, Carla Verena Hannig, Cornelia Liedtke
INTRODUCTION: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27920432/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#16
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919976/phase-i-study-of-triweekly-nab-paclitaxel-combined-with-s-1-in-patients-with-her2-negative-metastatic-breast-cancer
#17
Koichi Sakaguchi, Katsuhiko Nakatsukasa, Tetsuya Taguchi
AIM: We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). PATIENTS AND METHODS: This study was carried out with a 3+3 dose escalation design; patients with HER2-negative MBC received nab-paclitaxel at 180-260 mg/m(2) on day 1 and S-1 at 65-80 mg/m(2) daily on days 1-14, repeated every 3 weeks...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919974/a-phase-ii-study-of-adjuvant-chemotherapy-of-tegafur-uracil-for-patients-with-breast-cancer-with-her2-negative-pathologic-residual-invasive-disease-after-neoadjuvant-chemotherapy
#18
Satoru Tanaka, Mitsuhiko Iwamoto, Kosei Kimura, Yuko Takahashi, Hiyoya Fujioka, Nayuko Sato, Risa Terasawa, Kanako Kawaguchi, Ayana Ikari, Tomo Tominaga, Saki Maezawa, Nodoka Umezaki, Junna Matsuda, Kazuhisa Uchiyama
BACKGROUND: There is no consensus on the need for adjuvant chemotherapy for patients with pathological residual invasive breast cancer (non-pCR) after neoadjuvant chemotherapy (NAC). We evaluated the tolerability and safety of tegafur-uracil (UFT) as adjuvant chemotherapy for patients with human epidermal growth factor receptor 2-negative breast cancer that resulted in non-pCR after NAC. PATIENTS AND METHODS: We treated patients with 270 mg/m(2) UFT per day for 2 years after definitive surgery and radiotherapy, if necessary...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919965/bevacizumab-combined-with-docetaxel-or-paclitaxel-as-first-line-treatment-of-her2-negative-metastatic-breast-cancer
#19
Leena Tiainen, Minna Tanner, Outi Lahdenperä, Pia Vihinen, Arja Jukkola, Peeter Karihtala, Niina Paunu, Teppo Huttunen, Pirkko-Liisa Kellokumpu-Lehtinen
AIM: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. PATIENTS AND METHODS: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m(2) docetaxel (days 1 and 15, q4w) or 90 mg/m(2) paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919946/in-vivo-selection-of-intermediately-and-highly-malignant-variants-of-triple-negative-breast-cancer-in-orthotopic-nude-mouse-models
#20
Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M Hoffman
AIM: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MATERIALS AND METHODS: MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×10(7) cells/site) were initially injected subcutaneously in the flank of nude mice...
December 2016: Anticancer Research
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