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https://www.readbyqxmd.com/read/28625555/adjuvant-pertuzumab-improves-early-breast-cancer-outcomes
#1
Manjulika Das
No abstract text is available yet for this article.
June 15, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28615520/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#2
Patrizia Vici, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D'Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria, Teresa Gamucci
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611541/effectiveness-of-pertuzumab-trastuzumab-and-docetaxel-combination-neoadjuvant-chemotherapy-for-her2-positive-inflammatory-breast-cancer-a-case-report
#3
Yuji Yamashita, Yuko Tanaka, Seishi Kono, Meiko Nishimura, Toru Mukohara, Yukiko Morinaga, Shigeo Hara, Shintaro Takao
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. CASE REPORT: A 40-year-old woman was referred to our hospital for evaluation of an induration in the right breast, suspected to be breast cancer. The tumor was diagnosed as estrogen receptor-negative, progesterone receptor-negative, HER2-positive, T4dN3cM0 stage IIIc IBC with axillary lymph node metastasis. Rather than surgical intervention, we chose a systemic treatment approach with pertuzumab, trastuzumab, and docetaxel (PTD) combination therapy which was shown to be effective for HER2-positive IBC in the NeoSphere trial...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28592618/efficacy-and-safety-of-pertuzumab-and-trastuzumab-administered-in-a-single-infusion-bag-followed-by-vinorelbine-velvet-cohort-2-final-results
#4
Michael Andersson, José M López-Vega, Thierry Petit, Claudio Zamagni, Valerie Easton, Julia Kamber, Eleonora Restuccia, Edith A Perez
BACKGROUND: VELVET Cohort 1 demonstrated the applicability of pertuzumab, trastuzumab, and vinorelbine as an alternative first-line treatment regimen for patients with HER2-positive locally advanced or metastatic breast cancer (MBC) who cannot receive docetaxel. Co-infusion of pertuzumab and trastuzumab may reduce clinic time and medical resource utilization. We report results from Cohort 2, in which pertuzumab and trastuzumab were co-infused, followed by vinorelbine. PATIENTS AND METHODS: During cycle 1, patients with HER2-positive locally advanced or MBC received loading doses of pertuzumab (840 mg) and trastuzumab (8 mg/kg) on consecutive days, followed by vinorelbine (25 mg/m(2)) on days two and nine...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28588061/dual-her2-blockade-helps-prevent-breast-cancer-return
#5
(no author information available yet)
Adding pertuzumab to an adjuvant regimen of trastuzumab for women with early-stage HER2(+) breast cancer reduces the risk of disease recurrence, especially among those with node-positive and hormone receptor-negative disease. Results from the phase III APHINITY trial, which could help pertuzumab earn full approval for this indication, were presented at the 2017 American Society of Clinical Oncology Annual Meeting.
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28581356/adjuvant-pertuzumab-and-trastuzumab-in-early-her2-positive-breast-cancer
#6
Gunter von Minckwitz, Marion Procter, Evandro de Azambuja, Dimitrios Zardavas, Mark Benyunes, Giuseppe Viale, Thomas Suter, Amal Arahmani, Nathalie Rouchet, Emma Clark, Adam Knott, Istvan Lang, Christelle Levy, Denise A Yardley, Jose Bines, Richard D Gelber, Martine Piccart, Jose Baselga
Background Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. Methods We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab...
June 5, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28560579/multi-parametric-analysis-reveals-enhanced-g2-phase-arrest-of-an-optimized-anti-her2-antibody-to-inhibit-breast-cancer
#7
Chunxia Qiao, Xiaoling Lang, Longlong Luo, Shusheng Geng, Ming Lv, Jing Geng, Xinying Li, Jiannan Feng, Beifen Shen, Yan Li
OBJECTIVES: To find a "me-better" antibody by epitope-specific antibody optimization and multi-parametric analysis. RESULTS: Using epitope-specific library based on the commercial drug, Pertuzumab/2C4, we screened a novel human anti-HER2 antibody, MIL5, which has slightly higher affinity than the drug. MIL5 and 2C4 share the same epitope to bind HER2; however, MIL5 bound to HER2 His235-His245 more tightly than 2C4, which could be the main reason of its enhanced affinity...
May 30, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28552047/t-dm1-in-the-neo-adjuvant-treatment-of-her2-positive-breast-cancer-impact-of-the-kristine-trio-021-trial
#8
Alicia Fc Okines
BACKGROUND: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies. For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard component of neo-adjuvant therapy for HER2 positive breast cancer. Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which prevents HER2 receptor dimerisation...
May 28, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28533475/first-line-palliative-her2-targeted-therapy-in-her2-positive-metastatic-breast-cancer-is-less-effective-after-previous-adjuvant-trastuzumab-based-therapy
#9
Hánah N Rier, Mark-David Levin, Joost van Rosmalen, Monique M E M Bos, Jan C Drooger, Paul de Jong, Johanneke E A Portielje, Elisabeth M P Elsten, Albert-Jan Ten Tije, Stefan Sleijfer, Agnes Jager
BACKGROUND: Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-naïve patients (TN-group) in order to investigate the possibility of trastuzumab resistance...
May 22, 2017: Oncologist
https://www.readbyqxmd.com/read/28514745/combating-acquired-resistance-to-trastuzumab-by-an-anti-erbb2-fully-human-antibody
#10
Chao Wang, Lingfei Wang, Xiaojie Yu, Yajun Zhang, Yanchun Meng, Huajing Wang, Yang Yang, Jie Gao, Huafeng Wei, Jian Zhao, Cuihua Lu, Han Chen, Yanping Sun, Bohua Li
Trastuzumab resistance is a common problem that impedes the effectiveness of trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast cancers do not respond to trastuzumab (de novo resistance), and the majority of the trastuzumab-responsive cancers progress within 1 year (acquired resistance). Different mechanisms exist between de novo and acquired resistance. Innate resistance mechanisms are mainly independent of ErbB2 receptor activity, and acquired resistance involves with alterations depending on ErbB2 activity...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514732/structural-basis-of-a-novel-heterodimeric-fc-for-bispecific-antibody-production
#11
Hudie Wei, Haiyan Cai, Yuhao Jin, Pilin Wang, Qingqing Zhang, Yihui Lin, Weixiao Wang, Jinke Cheng, Naiyan Zeng, Ting Xu, Aiwu Zhou
Bispecific antibodies provide an efficient tool for combinational clinical therapy. Here we have engineered a heterodimeric Fc for bispecific antibodies production by combining the knob-into-hole and electrostatic steering strategies where a bulky hydrophobic residue Phe405 of the IgG CH3 interface is mutated to a charged residue Lys and Lys409 of the corresponding CH3 domain is mutated to Ala. The crystal structure of this Fc heterodimer solved here at 2.7Å resolution revealed how these two mutations resulted a complementary binding interface and explained why F405K mutation could effectively inhibit Fc homodimer formation during protein expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514302/safety-and-efficacy-evaluation-of-pertuzumab-in-patients-with-solid-tumors
#12
REVIEW
Chenjing Zhu, Wenwu Ling, Jing Zhang, Hui Gao, Kai Shen, Xuelei Ma
BACKGROUND: The development of targeted therapies benefits patients with certain markers in the treatment of breast cancer. Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. The Food and Drug Administration has approved pertuzumab in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer. METHODS: To assess the safety and efficacy profile of pertuzumab, we searched PubMed and Embase (articles from January 1966 to January 2015) using the keyword "pertuzumab"...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28493933/direct-estrogen-receptor-er-her-family-crosstalk-mediating-sensitivity-to-lumretuzumab-and-pertuzumab-in-er-breast-cancer
#13
Denis Collins, Wolfgang Jacob, Juan Miguel Cejalvo, Maurizio Ceppi, Ian James, Max Hasmann, John Crown, Andrés Cervantes, Martin Weisser, Birgit Bossenmaier
Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28476488/improving-pertuzumab-production-by-gene-optimization-and-proper-signal-peptide-selection
#14
Amin Ramezani, Elham Mahmoudi Maymand, Mahsa Yazdanpanah-Samani, Ahmad Hosseini, Fatemeh Sadat Toghraie, Abbas Ghaderi
Using proper signal peptide and codon optimization are important factors that must be considered when designing the vector to increase protein expression in Chinese Hamster Ovary (CHO) cells. The aim of the present study is to investigate how to enhance Pertuzumab production through heavy and light chain coding gene optimization and proper signal peptide selection. First, CHO-K1 cells were transiently transfected with whole-antibody-gene-optimized, variable-regions-optimized and non-optimized constructs and then we employed five different signal peptides to improve the secretion efficiency of Pertuzumab...
May 3, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28447218/pertuzumab-trastuzumab-ct-versus-trastuzumab-ct-therapy-for-her2-breast-cancer-results-from-the-prospective-neoadjuvant-breast-registry-symphony-trial-nbrst
#15
Peter Beitsch, Pat Whitworth, Paul Baron, Michael C Rotkis, Angela M Mislowsky, Paul D Richards, Mary K Murray, James V Pellicane, Carrie L Dul, Charles H Nash, Lisette Stork-Sloots, Femke de Snoo, Sarah Untch, Laura A Lee
BACKGROUND: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. METHODS: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U...
April 26, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28437161/randomized-phase-iii-trial-of-trastuzumab-plus-capecitabine-with-or-without-pertuzumab-in-patients-with-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-who-experienced-disease-progression-during-or-after-trastuzumab-based-therapy
#16
Ander Urruticoechea, Mohammed Rizwanullah, Seock-Ah Im, Antonio Carlos Sánchez Ruiz, István Láng, Gianluca Tomasello, Hannah Douthwaite, Tanja Badovinac Crnjevic, Sarah Heeson, Jennifer Eng-Wong, Montserrat Muñoz
Purpose To assess the efficacy and safety of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy and received a prior taxane. Patients and Methods Patients were randomly assigned to arm A: trastuzumab 8 mg/kg → 6 mg/kg once every 3 weeks plus capecitabine 1,250 mg/m(2) twice a day (2 weeks on, 1 week off, every 3 weeks); or arm B: pertuzumab 840 mg → 420 mg once every 3 weeks plus trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m(2) on the same schedule as arm A...
April 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#17
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28406988/peptide-probes-derived-from-pertuzumab-by-molecular-dynamics-modeling-for-her2-positive-tumor-imaging
#18
Xiaoliang Yang, Zihua Wang, Zhichu Xiang, Dan Li, Zhiyuan Hu, Wei Cui, Lingling Geng, Qiaojun Fang
A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a β hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28397880/glycoengineering-of-pertuzumab-and-its-impact-on-the-pharmacokinetic-pharmacodynamic-properties
#19
Cheng Luo, Song Chen, Na Xu, Chi Wang, Wen Bo Sai, Wei Zhao, Ying Chun Li, Xiao Jing Hu, Hong Tian, Xiang Dong Gao, Wen Bing Yao
Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396358/extracellular-matrix-integrin-signaling-promotes-resistance-to-combined-inhibition-of-her2-and-pi3k-in-her2-breast-cancer
#20
Ariella B Hanker, Mónica Valeria Estrada, Giampaolo Bianchini, Preston D Moore, Junfei Zhao, Feixiong Cheng, James P Koch, Luca Gianni, Darren R Tyson, Violeta Sánchez, Brent N Rexer, Melinda E Sanders, Zhongming Zhao, Thomas P Stricker, Carlos L Arteaga
PIK3CA mutations are associated with resistance to HER2-targeted therapies. We previously showed that HER2(+)/PIK3CA(H1047R) transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K. TPB-resistant tumors were generated by treating HER2(+)/PIK3CA(H1047R) tumor-bearing mice long term with the drug combination. RNA sequencing of TPB-resistant tumors revealed that extracellular matrix and cell adhesion genes, including collagen II (Col2a1), were markedly upregulated, accompanied by activation of integrin β1/Src...
June 15, 2017: Cancer Research
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