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Breast Cancer Herceptin

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https://www.readbyqxmd.com/read/29333017/correlation-of-hormone-receptor-and-human-epidermal-growth-factor-receptor-2-neu-expression-in-breast-cancer-with-various-clinicopathologic-factors
#1
Cherry Bansal, Aarti Sharma, Mukta Pujani, Meenu Pujani, Kiran Lata Sharma, A N Srivastava, U S Singh
Background: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. Aim of Study: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#2
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29305325/modeling-trastuzumab-related-cardiotoxicity-in-vitro-using-human-stem-cell-derived-cardiomyocytes
#3
Yosuke K Kurokawa, Michael R Shang, Rose T Yin, Steven C George
Trastuzumab (Herceptin®), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed...
January 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29281678/the-natural-compound-jatrophone-interferes-with-wnt-%C3%AE-catenin-signaling-and-inhibits-proliferation-and-emt-in-human-triple-negative-breast-cancer
#4
Iram Fatima, Ikbale El-Ayachi, Ling Taotao, M Angeles Lillo, Raya Krutilina, Tiffany N Seagroves, Tomasz W Radaszkiewicz, Miroslav Hutnan, Vitezslav Bryja, Susan A Krum, Fatima Rivas, Gustavo A Miranda-Carboni
Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC) are highly metastatic and are devoid of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease...
2017: PloS One
https://www.readbyqxmd.com/read/29245056/subcutaneous-trastuzumab-herceptin-versus-intravenous-trastuzumab-for-the-treatment-of-patients-with-her2-positive-breast-cancer-a-time-motion-and-cost-assessment-study-in-a-lean-operating-day-care-oncology-unit
#5
Wiebren A A Tjalma, Tom Van den Mooter, Tim Mertens, Valerie Bastiaens, Manon T Huizing, Konstantinos Papadimitriou
OBJECTIVE: The subcutaneous (SC) formulation of trastuzumab represents an alternative to the intravenous (IV) infusion in the treatment of patients with HER2-positive metastatic and early breast cancer. We compared the two formulations in terms of time and cost differential. STUDY DESING: We conducted a time, motion and cost assessment study in a lean operating day care oncology unit to determine and compare the time and costs of trastuzumab SC versus IV administration in patients with HER2-positive breast cancer...
December 7, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29216514/modulation-of-in-vitro-phagocytic-uptake-and-immunogenicity-potential-of-modified-herceptin%C3%A2-conjugated-plga-peg-nanoparticles-for-drug-delivery
#6
Apurva Badkas, Evan Frank, Zilan Zhou, Mina Jafari, Harish Chandra, Vishnu Sriram, Joo-Youp Lee, Jagjit S Yadav
There is an increasing interest in engineered nanoparticle (NP) conjugates for targeted and controlled drug delivery. However, the practical applications of these NP delivery vehicles remain constrained because of their reactivity with the body's immune system defenses resulting in undesirable off-target effects. In this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs conjugated to different quantities of the commercial antibody Herceptin® meant to target HER2-positive breast cancer cells were studied for their immune cell uptake and immunogenic properties (using murine macrophages and human dendritic cells)...
December 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29172171/trastuzumab-for-metastatic-breast-cancer-real-world-outcomes-from-an-australian-whole-of-population-cohort-2001-2016
#7
Benjamin Daniels, Belinda E Kiely, Sarah J Lord, Nehmat Houssami, Christine Y Lu, Robyn L Ward, Sallie-Anne Pearson
PURPOSE: Outcomes for patients treated in clinical trials may not reflect the experience in routine clinical care. We aim to describe the real-world treatment patterns and overall survival (OS) for women receiving trastuzumab for metastatic breast cancer (MBC). METHODS: Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for women in the Herceptin Program for HER2+MBC. We estimated time on trastuzumab and OS from first dispensing of trastuzumab for MBC and rates of cardiac monitoring prior to and during treatment...
November 21, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29163501/herceptin-enhances-the-antitumor-effect-of-natural-killer-cells-on-breast-cancer-cells-expressing-human-epidermal-growth-factor-receptor-2
#8
Xiao Tian, Feng Wei, Limei Wang, Wenwen Yu, Naining Zhang, Xinwei Zhang, Ying Han, Jinpu Yu, Xiubao Ren
Optimal adoptive cell therapy (ACT) should contribute to effective cancer treatment. The unique ability of natural killer (NK) cells to kill cancer cells independent of major histocompatibility requirement makes them suitable as ACT tools. Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2) monoclonal antibody, is used to treat HER2+ breast cancer. However, it has limited effectiveness and possible severe cardiotoxicity. Given that Herceptin may increase the cytotoxicity of lymphocytes, we explored the possible augmentation of NK cell cytotoxicity against HER2+ breast cancer cells by Herceptin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29069935/trastuzumab-modified-dm1-loaded-nanoparticles-for-her2-breast-cancer-treatment-an-in-vitro-and-in-vivo-study
#9
Ling Rong, Shuping Zhou, Xinkuang Liu, Amin Li, Tao Jing, Xueke Liu, Yinci Zhang, Shiyu Cai, Xiaolong Tang
BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2(+) breast cancer treatment, and its physical characterization and antitumor biological activity were investigated...
October 25, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29040918/tumor-cryoablation-in-combination-with-natural-killer-cells-therapy-and-herceptin-in-patients-with-her2-overexpressing-recurrent-breast-cancer
#10
Shuzhen Liang, Lizhi Niu, Kecheng Xu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In this study, we investigated the clinical benefits of a combination of tumor cryoablation with natural killer (NK) cells therapy and Herceptin for human epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May 2015 to May 2016, 48 patients who met the enrollment criteria were assigned to three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy group (group II) and cryoablation-NK cells therapy-Herceptin group (group III). Safety and short-term effects were evaluated...
December 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29038808/decoration-of-trastuzumab-with-short-oligonucleotides-synthesis-and-detailed-characterization
#11
A M Carvalho, A Manicardi, C Véliz Montes, S B Gunnoo, R J Schneider, A Madder
Trastuzumab (Herceptin®) is an FDA-approved therapeutic antibody currently employed in the treatment of metastatic stages of breast cancer. Herein, we propose a simple, fast and cost-effective methodology to conjugate trastuzumab with 22-mer 5' thiol-modified oligonucleotides using a bifunctional crosslinker. The conjugates were successfully characterized by MALDI-ToF MS and SDS-PAGE, obviating the need for enzymatic digestion and difficult chromatographic separations. Furthermore, ELISA was performed to ensure that trastuzumab activity is not affected by oligonucleotide conjugation...
October 31, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29017563/herceptin%C3%A2-trastuzumab-in-her2-positive-early-breast-cancer-protocol-for-a-systematic-review-and-cumulative-network-meta-analysis
#12
Florence R Wilson, Megan E Coombes, Quinlan Wylie, Mariya Yurchenko, Christine Brezden-Masley, Brian Hutton, Becky Skidmore, Chris Cameron
BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive disease that makes up about 20% of all invasive breast cancers. HER2+ breast cancer is associated with poor prognosis and high mortality rates, but the development of HER2-targeted therapies, such as originator trastuzumab (Herceptin®), has substantially improved patient survival. Numerous clinical trials and reviews have investigated the efficacy of HER2-targeted therapies over the past few decades; however, no study has specifically investigated the vast body of evidence on trastuzumab in comparison to chemotherapy regimens, endocrine therapies, and other targeted therapies...
October 10, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28963915/efficacy-and-safety-of-subcutaneous-trastuzumab-and-intravenous-trastuzumab-as-part-of-adjuvant-therapy-for-her2-positive-early-breast-cancer-final-analysis-of-the-randomised-two-cohort-prefher-study
#13
X Pivot, S Verma, L Fallowfield, V Müller, M Lichinitser, V Jenkins, A Sánchez Muñoz, Z Machackova, S Osborne, J Gligorov
AIM: To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin(®) SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin(®) [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks...
September 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#14
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28826287/docetaxel-loaded-nanostructured-lipid-carriers-functionalized-with-trastuzumab-herceptin-for-her2-positive-breast-cancer-cells
#15
Jaleh Varshosaz, Mohammad Ali Davoudi, Sara Rasoul-Amini
The aim of the present study was to prepare Herceptin targeted nanostructured lipid carriers (NLCs) of docetaxel (DTX). Herceptin was conjugated by chemical and physical methods to NLCs prepared by solvent extraction technique followed by probe sonication. Different types of fatty amines were used in construction of NLCs. The NLCs were characterized for their antibody coupling efficiency, particle size, zeta potential, polydispersity index, drug entrapment efficiency and drug release profiles. The toxicity of NLCs on MDA-MB-468 (HER2 negative receptor) and BT-474 (HER2 positive) breast cancer cell lines was evaluated by MTT assay...
August 21, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28783505/surface-modification-of-docetaxel-nanocrystals-with-her2-antibody-to-enhance-cell-growth-inhibition-in-breast-cancer-cells
#16
Jin-Seok Choi, Jeong-Sook Park
Here, we describe docetaxel nanocrystals (DTX-NCs) surface-modified with Herceptin(®) (HCT) for combination cancer therapy. Using nano-precipitation and adsorption method, DTX-NCs and HCT-DTX-NCs were successfully prepared. The morphologies of DTX-NCs and HCT-DTX-NCs were characterized by field emission scanning electron microscopy (FE-SEM). The particle size and surface charge were evaluated by zeta-sizer and zeta-potential, respectively. Moreover, DTX-NCs and HCT-DTX-NCs were evaluated in terms of an in vitro drug release, cellular uptake and cytotoxicity...
July 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28663873/autofluorescence-imaging-captures-heterogeneous-drug-response-differences-between-2d-and-3d-breast-cancer-cultures
#17
T M Cannon, A T Shah, M C Skala
Two-photon microscopy of cellular autofluorescence intensity and lifetime (optical metabolic imaging, or OMI) is a promising tool for preclinical drug development. OMI, which exploits the endogenous fluorescence from the metabolic coenzymes NAD(P)H and FAD, is sensitive to changes in cell metabolism produced by drug treatment. Previous studies have shown that drug response, genetic expression, cell-cell communication, and cell signaling in 3D culture match those of the original in vivo tumor, but not those of 2D culture...
March 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28625777/safety-and-tolerability-of-subcutaneous-trastuzumab-for-the-adjuvant-treatment-of-human-epidermal-growth-factor-receptor-2-positive-early-breast-cancer-safeher-phase-iii-study-s-primary-analysis-of-2573-patients
#18
MULTICENTER STUDY
J Gligorov, B Ataseven, M Verrill, M De Laurentiis, K H Jung, H A Azim, N Al-Sakaff, S Lauer, M Shing, X Pivot
AIM: To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin(®) SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). METHODS: Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28624696/superimposable-outcomes-for-sequential-and-concomitant-administration-of-adjuvant-trastuzumab-in%C3%A2-her2-positive-breast-cancer-results-from-the-signal-phare-prospective-cohort
#19
RANDOMIZED CONTROLLED TRIAL
Xavier Pivot, Pierre Fumoleau, Jean-Yves Pierga, Suzette Delaloge, Hervé Bonnefoi, Thomas Bachelot, Christelle Jouannaud, Hugues Bourgeois, Maria Rios, Patrick Soulié, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Pierre Kerbrat, David Cox, Céline Faure-Mercier, Iris Pauporte, Joseph Gligorov, Elsa Curtit, Julie Henriques, Sophie Paget-Bailly, Gilles Romieu
AIM: Adjuvant clinical trials in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer have assessed either sequential or concomitant incorporation of trastuzumab with chemotherapy; only the North Central Cancer Treatment Group (NCCTG)-N9831 trial prospectively compared both modalities. In routine trastuzumab has been incorporated into a concurrent regimen with taxane chemotherapy instead of sequential modality on the basis of a positive risk-benefit ratio. This present study assessed sequential versus concomitant administration of adjuvant trastuzumab...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28623430/a-phase-i-ii-study-of-suberoylanilide-hydroxamic-acid-saha-in-combination-with-trastuzumab-herceptin-in-patients-with-advanced-metastatic-and-or-local-chest-wall-recurrent-her2-amplified-breast-cancer-a-trial-of-the-ecog-acrin-cancer-research-group-e1104
#20
Lori J Goldstein, Fengmin Zhao, Molin Wang, Ramona F Swaby, Joseph A Sparano, Neal J Meropol, Kapil N Bhalla, Christine M Pellegrino, R Katherine Alpaugh, Carla I Falkson, Paula Klein, George W Sledge
PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease...
September 2017: Breast Cancer Research and Treatment
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