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breast cancer pertuzumab

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
Ariella B Hanker, Monica Valeria Estrada, Giampaolo Bianchini, Preston D Moore, Junfei Zhao, Feixiong Cheng, Luca Gianni, James P Koch, Darren R Tyson, Violeta Sanchez, Brent N Rexer, Melinda Sanders, Zhongming Zhao, Thomas 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) mice long-term with the drug combination. RNA-sequencing of TPB-resistant tumors revealed that extracellular matrix (ECM) and cell adhesion genes, including collagen II (Col2a1), were markedly upregulated, accompanied by activation of integrin β1/Src...
April 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28381415/her2-overexpressing-breast-cancers-amplify-fgfr-signaling-upon-acquisition-of-resistance-to-dual-therapeutic-blockade-of-her2
#7
Ariella B Hanker, Joan G Garrett, Monica Valeria Estrada, Preston D Moore, Paula G Ericsson, James P Koch, Emma Langley, Sharat Singh, Phillip S Kim, Garrett M Frampton, Eric M Sanford, Philip Owns, Jennifer Becker, M Reid Groseclose, Stephen Castellino, Heikki Joensuu, Jens Huober, Jan C Brase, Majjaj Samira, Sylvain Brohée, David Venet, David Brown, José Baselga, Martine Piccart, Christos Sotiriou, Carlos L Arteaga
Dual blockade of HER2 with trastuzumab and lapatinib or pertuzumab has been shown to be superior to single-agent trastuzumab. However, a significant fraction of HER2-overexpressing (HER2+) breast cancers escape from these drug combinations. In this study, we sought to discover the mechanisms of acquired resistance to the combination of lapatinib + trastuzumab.<br /><br />Experimental Design: HER2+ BT474 xenografts were treated with lapatinib + trastuzumab long-term until resistance developed. Potential mechanisms of acquired resistance were evaluated in lapatinib + trastuzumab-resistant (LTR) tumors by targeted capture next-generation sequencing...
April 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28377827/anti-yo-mediated-paraneoplastic-cerebellar-degeneration-associated-with-pseudobulbar-affect-in-a-patient-with-breast-cancer
#8
Allison N Martin, Patrick M Dillon, David E Jones, David R Brenin, David A Lapides
Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28373460/a-locally-advanced-breast-cancer-that-achieved-pcr-with-pertuzumab-trastuzumab-and-docetaxel-case-report
#9
Yuka Inoue, Nami Yamashita, Eriko Tokunaga, Kimihiro Tanaka, Hiroki Ueo, Hiroshi Saeki, Eiji Oki, Hidetaka Yamamoto, Yoshihiko Maehara
We herein report a case of locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that achieved a pathological complete response (pCR) with pertuzumab, trastuzumab and docetaxel therapy. A 70-year-old female presented with an elastic hard mass, 5.0 cm in diameter with broad redness and edema of the skin in her right breast. Swollen lymph nodes were also recognized in the right axilla. The pathological diagnosis was invasive ductal carcinoma and its biological character was estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, HER2 3+ and Ki-67 index 60%...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28365969/lapatinib-plus-capecitabine-in-metastatic-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-patients-that-received-prior-therapy-with-trastuzumab-and-pertuzumab-better-option-than-t-dm1
#10
Kadri Altundag
No abstract text is available yet for this article.
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28347625/combination-of-radiotherapy-and-double-blockade-her2-with-pertuzumab-and-trastuzumab-for-her2-positive-metastatic-or-locally-recurrent-unresectable-and-or-metastatic-breast-cancer-assessment-of-early-toxicity
#11
Z Ajgal, S de Percin, V Diéras, J Y Pierga, F Campana, A Fourquet, Y M Kirova
BACKGROUND AND PURPOSES: We evaluate the early toxicity of concurrent use of radiotherapy, pertuzumab and trastuzumab in patients with HER2-positive metastatic or locally recurrent unresectable breast cancer. PATIENTS AND METHODS: A retrospective study was performed in a population of 23 consecutive patients between 2013 and 2015. Radiotherapy was performed on the chest area or metastatic sites during maintenance with pertuzumab and trastuzumab after six cycles of pertuzumab, trastuzumab and docetaxel...
March 24, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28341761/cardiac-safety-of-dual-anti-her2-therapy-in-the-neoadjuvant-setting-for-treatment-of-her2-positive-breast-cancer
#12
Anthony F Yu, Jasmeet C Singh, Rui Wang, Jennifer E Liu, Anne Eaton, Kevin C Oeffinger, Richard M Steingart, Clifford A Hudis, Chau T Dang
BACKGROUND: Trastuzumab and pertuzumab are approved for the neoadjuvant treatment of human epidermal growth receptor 2 (HER2)-positive breast cancer, but cardiac safety data is limited. We report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy. METHODS: Fifty-seven patients treated with neoadjuvant dose-dense AC-THP followed by adjuvant trastuzumab-based therapy between September 1, 2013, and March 1, 2015, were identified...
March 24, 2017: Oncologist
https://www.readbyqxmd.com/read/28266967/liver-resection-for-breast-cancer-liver-metastases-a-cost-utility-analysis
#13
Gaya Spolverato, Alessandro Vitale, Fabio Bagante, Roisin Connolly, Timothy M Pawlik
OBJECTIVE: To estimate the cost-effectiveness of liver resection followed by adjuvant systemic therapy relative to systemic therapy alone for patients with breast cancer liver metastasis. BACKGROUND: Data on cost-effectiveness of liver resection for advanced breast cancer with liver metastasis are lacking. METHODS: A decision-analytic Markov model was constructed to evaluate the cost-effectiveness of liver resection followed by postoperative conventional systemic therapy (strategy A) versus conventional therapy alone (strategy B) versus newer targeted therapy alone (strategy C)...
April 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28259011/clinical-use-of-biomarkers-in-breast-cancer-updated-guidelines-from-the-european-group-on-tumor-markers-egtm
#14
REVIEW
M J Duffy, N Harbeck, M Nap, R Molina, A Nicolini, E Senkus, F Cardoso
Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour...
April 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28236776/evolving-landscape-of-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-treatment-and-the-future-of-biosimilars
#15
REVIEW
Christian Jackisch, Philip Lammers, Ira Jacobs
Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve...
April 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28228709/targeted-therapies-in-her2-overexpressing-metastatic-breast-cancer
#16
REVIEW
Soumaya Labidi, Nesrine Mejri, Aymen Lagha, Nouha Daoud, Houda El Benna, Mehdi Afrit, Hamouda Boussen
Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and poorer survival. Multiple anti-HER2 targeted therapies have dramatically changed management and outcome of this subgroup, both in adjuvant and metastatic settings. Despite the improvement of survival thanks to trastuzumab, unclear mechanisms of resistance occur, which has led to the development of new anti-HER2 therapies such as lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1)...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228705/her2-orientated-therapy-in-early-and-metastatic-breast-cancer
#17
REVIEW
Severine Iborra, Elmar Stickeler
Due to the enhanced understanding of molecular oncology and signaling pathways in breast cancer (BC), therapy management has undergone a major transformation, especially with the emergence of treatment tailored to individual disease characteristics. In the case of HER2-positive early or metastatic BC, targeted therapies are well established and remain a major focus of ongoing research. The introduction of anti-HER2 biologicals such as trastuzumab, pertuzumab, and T-DM1 has made targeted and personalized treatment possible and has clearly improved disease-free and overall survival in patients with HER2-positive BC...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28199966/does-dual-her-2-blockade-treatment-increase-the-risk-of-severe-toxicities-of-special-interests-in-breast-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#18
Shuai Hao, Wuguo Tian, Bo Gao, Yan Jiang, Xiaohua Zhang, Shu Zhang, Lingji Guo, Jianjie Zhao, Gang Zhang, Chunyan Hu, Jie Yan, Donglin Luo
Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196634/objective-domain-specific-her2-measurement-in-uterine-and-ovarian-serous-carcinomas-and-its-clinical-significance
#19
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...
April 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28183321/biomarker-analysis-of-the-neosphere-study-pertuzumab-trastuzumab-and-docetaxel-versus-trastuzumab-plus-docetaxel-pertuzumab-plus-trastuzumab-or-pertuzumab-plus-docetaxel-for-the-neoadjuvant-treatment-of-her2-positive-breast-cancer
#20
Giampaolo Bianchini, Astrid Kiermaier, Giulia Valeria Bianchi, Young-Hyuck Im, Tadeusz Pienkowski, Mei-Ching Liu, Ling-Ming Tseng, Mitch Dowsett, Lila Zabaglo, Sarah Kirk, Tania Szado, Jennifer Eng-Wong, Lukas C Amler, Pinuccia Valagussa, Luca Gianni
BACKGROUND: NeoSphere showed significantly higher pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and docetaxel compared with trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel. We assessed associations between human epidermal growth factor receptor 2 (HER2) pathway-related biomarkers and clinical outcome in response to these regimens. METHODS: Tumor, serum, and whole blood samples were collected at baseline and post neoadjuvant treatment before surgery...
February 9, 2017: Breast Cancer Research: BCR
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