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https://www.readbyqxmd.com/read/29772459/tyrosine-kinase-inhibitors-for-brain-metastases-in-her2-positive-breast-cancer
#1
REVIEW
Renata Duchnowska, Sibylle Loibl, Jacek Jassem
Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy...
May 9, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29751334/treatment-of-advanced-her2-positive-breast-cancer-2018-and-beyond
#2
REVIEW
Noam Pondé, Mariana Brandão, Georges El-Hachem, Emilie Werbrouck, Martine Piccart
In the 1980s the importance of HER2 signalling to the aberrant behaviour of a subset of breast cancer cells was recognized for the first time and, consequently, a hitherto unknown subtype of breast cancer - HER2-positive (HER2+) breast cancer was identified. The development of the anti-HER2 class of drugs, first with trastuzumab, followed closely by lapatinib, pertuzumab, and T-DM1, has improved outcomes dramatically. Nevertheless, metastatic HER2+ breast cancer remains an incurable disease and new therapeutic options are needed...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29739815/impact-of-hormone-receptor-status-on-the-efficacy-of-her2-targeted-treatment
#3
Bin Zhao, Hong Zhao, Jiaxin Zhao
The introduction of human epidermal growth factor receptor 2 (HER2)-targeted drugs into routine clinical practice has a dramatic effect on the outlook for patients with HER2-positive breast cancer (BC). However, the association between efficacy of HER2-targeted therapy and hormone receptor (HR) status is still unclear. Here we conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue in both neoadjuvant and adjuvant settings. PubMed and EMBASE were searched from inception to October 2017 for studies involving trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine and neratinib...
June 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29725336/tribody-her2-2-xcd16-is-more-effective-than-trastuzumab-in-enhancing-%C3%AE-%C3%AE-t-cell-and-natural-killer-cell-cytotoxicity-against-her2-expressing-cancer-cells
#4
Hans H Oberg, Christian Kellner, Daniel Gonnermann, Susanne Sebens, Dirk Bauerschlag, Martin Gramatzki, Dieter Kabelitz, Matthias Peipp, Daniela Wesch
An enhanced expression of human epidermal growth factor receptor 2 (HER2, ErbB2) often occurs in an advanced stage of breast, ovarian, gastric or esophageal cancer, and pancreatic ductal adenocarcinoma (PDAC). Commonly, HER2 expression is associated with poor clinical outcome or chemoresistance in ovarian and breast cancer patients. Treatment with humanized anti-HER2 monoclonal antibodies, such as trastuzumab or pertuzumab, has improved the outcome of patients with HER2-positive metastatic gastric or breast cancer, but not all patients benefit...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29719406/cardiotoxic-effects-of-the-novel-approved-anti-erbb2-agents-and-reverse-cardioprotective-effects-of-ranolazine
#5
Claudia De Lorenzo, Rolando Paciello, Gennaro Riccio, Domenica Rea, Antonio Barbieri, Carmela Coppola, Nicola Maurea
Purpose: Pertuzumab, a novel anti-epidermal growth factor receptor 2 humanized monoclonal antibody, and trastuzumab-emtansine (TDM1), a novel antibody-drug conjugate made up of trastuzumab covalently linked to the highly potent microtubule inhibitory agent DM1, have been recently approved by the US Food and Drug Administration for increasing the efficiency and safety of breast cancer therapy with trastuzumab. We investigated for the first time the potential cardiotoxic effects of pertuzumab and TDM1, which are not yet fully elucidated, and we tested whether ranolazine could blunt their cardiotoxicity...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29714649/personalized-therapy-based-on-sequential-molecular-analysis-leads-to-30-months-of-survival-in-a-patient-with-diffuse-unresectable-gastric-linitis-plastica
#6
Linda Mahjoubi, Fabiola Cecchi, Christophe Massard, Fabio Calabro, Anas Gazzah, Rastislav Bahleda, Philippe Jamme, Maximiliano Gelli, Diane Goere, Ludovic Lacroix, Julien Adam, Lukas Heukamp, Patrizia Trenta, Todd Hembrough, Jean-Charles Soria, Cora Sternberg, Michel Ducreux
INTRODUCTION: Diffuse gastric cancer is associated with poor prognosis. We report a patient with metastatic gastric linitis plastica harboring human epidermal growth factor receptor 2 ( HER2) activating mutation and HER2 amplification. CASE DESCRIPTION: The patient received 5-fluorouracil/folinic acid and oxaliplatin combined with trastuzumab/pertuzumab, resulting in disease control for 8 months. Second-line therapy with nivolumab and trastuzumab/pertuzumab was well-tolerated, with macroscopic peritoneal response...
March 1, 2018: Tumori
https://www.readbyqxmd.com/read/29670855/current-therapies-for-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-patients
#7
REVIEW
Alexey A Larionov
The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29650905/-a-case-of-her2-positive-breast-cancer-with-liver-metastases-showing-three-years-of-complete-response-to-combination-therapy-with-trastuzumabplus-pertuzumab
#8
Yuri Fujimoto, Kazushige Yamaguchi, Ayako Ueno, Reo Sakurai, Yoshio Nagahisa, Shiro Imai, Kazuyuki Kawamoto
A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29615305/early-stage-her2-positive-breast-cancers-not-achieving-a-pcr-from-neoadjuvant-trastuzumab-or-pertuzumab-based-regimens-have-an-immunosuppressive-phenotype
#9
Jeremy Force, Lynn J Howie, Sara E Abbott, Rex Bentley, P Kelly Marcom, Gretchen Kimmick, Kelly Westbrook, Sarah L Sammons, Michelle Parks, Donna L Topping, Ryan Emerson, Gloria Broadwater, Terry Hyslop, Kimberly L Blackwell, Smita K Nair
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+ ) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+ , CD8+ , FoxP3+ , and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor β (TCRβ) rearrangements and TCRβ clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens...
February 24, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29615076/use-of-the-tumor-infiltrating-cd8-to-foxp3-lymphocyte-ratio-in-predicting-treatment-responses-to-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#10
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29599915/pertuzumab-trastuzumab-and-eribulin-mesylate-therapy-for-previously-treated-advanced-her2-positive-breast-cancer-a-feasibility-study-with-analysis-of-biomarkers
#11
Yasutaka Tono, Mikiya Ishihara, Yoshihiro Miyahara, Satoshi Tamaru, Hiroyasu Oda, Yoshiki Yamashita, Isao Tawara, Hiroaki Ikeda, Hiroshi Shiku, Toshiro Mizuno, Naoyuki Katayama
The standard treatment for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is the triple combination of pertuzumab, trastuzumab and docetaxel, but some patients cannot tolerate taxane. To explore a non-taxane triple therapy, we conducted a feasibility study of pertuzumab, trastuzumab and eribulin mesylate (PTE) therapy for previously treated advanced HER2-positive breast cancer with analyses of quality of life and biomarkers. Ten patients were enrolled, two of whom had a history of docetaxel allergy...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29599351/analysis-of-her-family-her1-4-expression-as-a-biomarker-in-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#12
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Chemotherapy with trastuzumab, pertuzumab and docetaxel (TPD regimen) is now strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER)2-positive breast cancer. In this study, we analyzed the expression of HER 1-4 proteins, and investigated whether or not their expression was predictive of the response of advanced HER2-positive breast cancer to chemotherapy with the TPD regimen. PATIENTS AND METHODS: The study consisted of 29 cases in which TPD regimen chemotherapy was carried out from September 2013 to November 2015...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29593727/effect-of-vh-vl-families-in-pertuzumab-and-trastuzumab-recombinant-production-her2-and-fc%C3%AE-iia-binding
#13
Wei-Li Ling, Wai-Heng Lua, Jun-Jie Poh, Joshua Yi Yeo, David Philip Lane, Samuel Ken-En Gan
Many therapeutic antibodies are humanized from animal sources. In the humanization process, complementarity determining region grafting is tedious and highly prone to failure. With seven known VH families, and up to six known κ VL families, there are choices aplenty. However, the functions of these families remain largely enigmatic. To study the role of these V-region families, we made 84 recombinant combinations of the various VH and VL family whole IgG1 variants of both Trastuzumab and Pertuzumab. We managed to purify 66 of these to investigate the biophysical characteristics: recombinant protein production, and both Her2 and FcγIIA binding...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29550255/microenvironment-mediated-mechanisms-of-resistance-to-her2-inhibitors-differ-between-her2-breast-cancer-subtypes
#14
Spencer S Watson, Mark Dane, Koei Chin, Zuzana Tatarova, Moqing Liu, Tiera Liby, Wallace Thompson, Rebecca Smith, Michel Nederlof, Elmar Bucher, David Kilburn, Matthew Whitman, Damir Sudar, Gordon B Mills, Laura M Heiser, Oliver Jonas, Joe W Gray, James E Korkola
Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental signals influence resistance, we monitored TKI-treated breast cancer cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations of 56 soluble and 46 matrix microenvironmental proteins on basal-like HER2+ (HER2E) or luminal-like HER2+ (L-HER2+) cells treated with the TKIs lapatinib or neratinib...
February 21, 2018: Cell Systems
https://www.readbyqxmd.com/read/29468855/major-clinical-research-advances-in-gynecologic-cancer-in-2017
#15
REVIEW
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29466887/access-to-anti-cancer-drugs-in-india-is-there-a-need-to-revise-reimbursement-policies
#16
Gertruud Haitsma, Himanshu Patel, Parthasarathi Gurumurthy, Maarten J Postma
BACKGROUND: The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India. METHODS: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines...
February 26, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29456473/adverse-events-of-trastuzumab-emtansine-t-dm1-in-the-treatment-of-her2-positive-breast-cancer-patients
#17
REVIEW
Lidia Kowalczyk, Rupert Bartsch, Christian F Singer, Alex Farr
The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29437532/using-a-dihydrofolate-reductase-based-strategy-for-producing-the-biosimilar-version-of-pertuzumab-in-cho-s-cells
#18
Amin Ramezani, Abbas Ghaderi
Targeted therapy using monoclonal antibodies (mAbs) against epidermal growth factor receptor-2 (ErbB2) has been utilized for the treatment of breast cancer, recently. Pertuzumab, one of the anti-ErbB2 mAbs, was approved by FDA in 2012 for the treatment of metastatic breast cancer. The aim of this study was to produce biosimilar version of pertuzumab in Chinese hamster ovary (CHO)-S cell line, and compare its ErbB2-binding and biological activities, with commercial drug, Perjeta. To this end, a dihydrofolate reductase (DHFR)-based strategy was used to produce a CHO-S stable cell pool capable of producing high levels of pertuzumab...
February 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29433963/pertuzumab-and-trastuzumab-with-or-without-metronomic-chemotherapy-for-older-patients-with-her2-positive-metastatic-breast-cancer-eortc-75111-10114-an-open-label-randomised-phase-2-trial-from-the-elderly-task-force-breast-cancer-group
#19
Hans Wildiers, Konstantinos Tryfonidis, Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara Brouwers, Sevilay Altintas, Nathan Touati, Fatima Cardoso, Etienne Brain
BACKGROUND: Despite the high incidence of metastatic breast cancer and its related mortality in the elderly population, our knowledge about optimal treatment for older patients with cancer is far from adequate. We aimed to evaluate the efficacy of dual anti-HER2 treatment with or without metronomic chemotherapy in older patients with HER2-positive metastatic breast cancer. METHODS: We did a multicentre, open-label, randomised, phase 2 trial in 30 centres from eight countries in Europe, in patients with histologically proven, HER2-positive metastatic breast cancer, without previous chemotherapy for metastatic disease, who were 70 years or older, or 60 years or older with confirmed functional restrictions defined by protocol, and had a life expectancy of more than 12 weeks and a performance status according to WHO scale of 0-3...
March 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29426804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-cell-surface-receptors-and-associated-signaling-pathways
#20
REVIEW
J Aguilar-Company, M Fernández-Ruiz, R García-Campelo, A C Garrido-Castro, I Ruiz-Camps
BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations...
February 7, 2018: Clinical Microbiology and Infection
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