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https://www.readbyqxmd.com/read/29052609/neuro-ophthalmic-side-effects-of-molecularly-targeted-cancer-drugs
#1
REVIEW
M T Bhatti, A K S Salama
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity...
October 20, 2017: Eye
https://www.readbyqxmd.com/read/29052527/negative-genic-switch-of-her-2-in-the-primary-tumor-instead-of-the-synchronous-metastatic-nodal-lesions-after-neoadjuvant-chemotherapy-in-a-patient-with-primary-her2-positive-breast-cancer
#2
Hao-Ran Chen, Yu-Tuan Wu, Qiu-Bo Yu, Ya-Ying Yang, Yu-Xian Wei, Hong-Yuan Li, Kai-Nan Wu, Ling-Quan Kong
BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting. CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC...
October 19, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29048687/sp1-promotes-tumor-angiogenesis-and-invasion-by-activating-vegf-expression-in-an-acquired-trastuzumab%C3%A2-resistant-ovarian-cancer-model
#3
Feng Su, Jing Geng, Xinying Li, Chuan Qiao, Longlong Luo, Jiannan Feng, Xinjun Dong, Ming Lv
Ovarian cancer is one of the most common gynecologic cancers and the leading cause of mortality in women worldwide. HER2/neu is overexpressed in various types of cancers and is most commonly associated with decreased survival. Trastuzumab is a humanized anti-HER2 monoclonal antibody for the treatment of HER2-positive breast cancers. However, primary and/or acquired resistance occurs in up to 62% patients during the first year of treatment. Vascular endothelial growth factor (VEGF) is a well‑known angiogenesis factor involved in many physiological and pathological processes...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048656/nrg1-dependent-activation-of-her3-induces-primary-resistance-to-trastuzumab-in-her2-overexpressing-breast-cancer-cells
#4
Liuting Yang, Yingying Li, Enyun Shen, Fengqi Cao, Li Li, Xiaojin Li, Xuejiang Wang, Seyed Kariminia, Bingmei Chang, Hongzhong Li, Qin Li
This study was conducted to determine the role of neuregulin 1 (NRG1)-dependent human epidermal growth factor receptor 3 (HER3) activation in trastuzumab primary resistance, and to observe the inhibitory effect of HER3 monoclonal antibody on HER2-overexpressing breast cancer cells. BT474 cells (trastuzumab sensitive) and MDA-MB-453 cells (trastuzumab resistant) were first stimulated with NRG1 and then treated with either trastuzumab, HER3 antibody, or a combination of both. The expression of phospho human epidermal growth factor receptor 2 (p-HER2), phospho human epidermal growth factor receptor 3 (p-HER3), phospho protein kinase B (p-Akt) and phospho mitogen-activated protein kinase (p-MAPK) were detected by western blotting...
September 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29045543/a-predictive-model-of-pathological-response-based-on-tumor-cellularity-and-tumor-infiltrating-lymphocytes-celtil-in-her2-positive-breast-cancer-treated-with-chemo-free-dual-her2-blockade
#5
P Nuciforo, T Pascual, J Cortés, A Llombart-Cussac, R Fasani, L Paré, M Oliveira, P Galvan, N Martínez, B Bermejo, M Vidal, S Pernas, R López, M Muñoz, I Garau, L Manso, J Alarcón, E Martínez, V Rodrik-Outmezguine, J C Brase, P Villagrasa, A Prat, E Holgado
Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathological complete response (pCR) and improved outcomes in HER2-positive early breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown. Patients and methods: The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab (and hormonal therapy if hormone receptor [HR]-positive) for 18 weeks...
October 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29043411/population-pharmacokinetics-of-trastuzumab-emtansine-in-previously-treated-patients-with-her2-positive-advanced-gastric-cancer-agc
#6
Shang-Chiung Chen, Matts Kagedal, Yuying Gao, Bei Wang, Marie-Laurence Harle-Yge, Sandhya Girish, Jin Jin, Chunze Li
PURPOSE: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising trastuzumab conjugated via a stable thioether linker to DM1, a highly potent cytotoxic agent. A population pharmacokinetics (PK) analysis was performed to characterize T-DM1 PK and evaluate the impact of patient characteristics on T-DM1 PK in previously treated patients with HER2-positive advanced gastric cancer (AGC). METHODS: Following T-DM1 weekly or every three weeks dosing, T-DM1 concentration measurements (n = 780) were collected from 136 patients in the GATSBY (NCT01641939) study and analyzed using nonlinear mixed effects modeling...
October 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29042085/advances-in-the-management-of-her2-positive-early-breast-cancer
#7
REVIEW
José Baselga, Robert E Coleman, Javier Cortés, Wolfgang Janni
While trastuzumab is firmly established as the cornerstone of therapy for both early and advanced breast cancer expressing human epidermal growth factor receptor 2 (HER2), many patients either do not respond to trastuzumab treatment or progress following therapy. Improved understanding of breast cancer biology, particularly the complex signaling interactions managed by the HER family of receptors, have resulted in development of several novel HER2-directed therapies and combinations. This article will review the novel approaches to HER2 targeting that have been developed in recent years, with particular focus on results from these approaches in early breast cancer, and will discuss strategies to improve the tolerability of HER2-directed therapies, including prevention of cardiac toxicity and diarrhea...
October 4, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29038808/decoration-of-trastuzumab-with-short-oligonucleotides-synthesis-and-detailed-characterization
#8
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 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29037983/safety-pharmacokinetics-and-antitumour-activity-of-trastuzumab-deruxtecan-ds-8201-a-her2-targeting-antibody-drug-conjugate-in-patients-with-advanced-breast-and-gastric-or-gastro-oesophageal-tumours-a-phase-1-dose-escalation-study
#9
Toshihiko Doi, Kohei Shitara, Yoichi Naito, Akihiko Shimomura, Yasuhiro Fujiwara, Kan Yonemori, Chikako Shimizu, Tatsunori Shimoi, Yasutoshi Kuboki, Nobuaki Matsubara, Atsuko Kitano, Takahiro Jikoh, Caleb Lee, Yoshihiko Fujisaki, Yusuke Ogitani, Antoine Yver, Kenji Tamura
BACKGROUND: Antibody-drug conjugates have emerged as a powerful strategy in cancer therapy and combine the ability of monoclonal antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. Trastuzumab deruxtecan (also known as DS-8201) is an antibody-drug conjugate comprised of a humanised antibody against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor payload. We assessed its safety and tolerability in patients with advanced breast and gastric or gastro-oesophageal tumours...
October 13, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29037469/management-of-patients-with-adenocarcinoma-or-squamous-cancer-of-the-esophagus
#10
David H Ilson, Richard Hillegersberg
Esophageal cancer is characterized by the early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive peri-operative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit...
October 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29034239/hepatoid-adenocarcinoma-of-the-stomach-a-challenging-diagnostic-and-therapeutic-disease-through-a-case-report-and-review-of-the-literature
#11
Najla Fakhruddin, Hisham F Bahmad, Tarek Aridi, Yara Yammine, Rami Mahfouz, Fouad Boulos, Ahmad Awada, Fadi Farhat
Hepatoid adenocarcinoma of the stomach (HAS) is a rare aggressive tumor with hepatocellular differentiation. HAS often produces alpha fetoprotein (AFP) and metastasizes to the lymph nodes and the liver. Molecular studies revealed Her2 amplification and overexpression, association with p53 mutations, but no association with KRAS mutations. EGFR and BRAF mutations have not yet been evaluated in hepatoid carcinoma of the stomach so far. Hereby, we present a case of a 41-year-old female patient with HAS with high AFP level and liver metastases...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29029640/breast-carcinomas-with-low-amplified-equivocal-her2-by-ish-potential-supporting-role-of-multiplex-ligation-dependent-probe-amplification
#12
Cristiana Ercolani, Caterina Marchiò, Anna Di Benedetto, Alessandra Fabi, Letizia Perracchio, Patrizia Vici, Francesca Sperati, Simonetta Buglioni, Vincenzo Arena, Edoardo Pescarmona, Anna Sapino, Irene Terrenato, Marcella Mottolese
BACKGROUND: This is a retrospective cross sectional study aimed to verify whether Multiplex Ligation-dependent Probe Amplification (MLPA), a quantitative molecular assay, may represent a valuable reflex test in breast cancer with equivocal HER2 expression by immunohistochemistry and HER2 gene signals/nucleus (s/n) ranging between 4.0 and 5.9 by in situ hybridization. METHODS: A series of 170 breast carcinomas scored as 2+ for HER2 expression by immunohistochemistry, were selected from our files and analyzed in parallel by silver in situ hybridization and by MLPA...
October 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29027290/pertuzumab-and-trastuzumab-infusion-related-cytokine-release-syndrome-in-a-chemotherapy-naive-patient-with-metastatic-breast-cancer
#13
Adonice Khoury, Vikas Parihar, Lillie O'steen, Kartikeya Cherabuddi
Pertuzumab is a monoclonal antibody that targets and down regulates HER-2/neu expression in ductal breast tumors. Other HER-2/neu monoclonal antibodies, particularly trastuzumab, have been implicated to induce infusion related reactions such as cytokine release syndrome (CRS). Here, we report a case of pertuzumab associated CRS prior to infusion of trastuzumab which warranted hospitalization for symptom management.
October 13, 2017: Breast Journal
https://www.readbyqxmd.com/read/29022084/exposure-response-analyses-of-trastuzumab-emtansine-in-patients-with-her2-positive-advanced-breast-cancer-previously-treated-with-trastuzumab-and-a-taxane
#14
Chunze Li, Bei Wang, Shang-Chiung Chen, Russell Wada, Dan Lu, Xin Wang, Daniel Polhamus, Jonathan French, Shweta Vadhavkar, Alexander Strasak, Melanie Smitt, Amita Joshi, Meghna Samant, Angelica Quartino, Jin Jin, Sandhya Girish
PURPOSE: In the phase III EMILIA study, trastuzumab emtansine (T-DM1) significantly improved progression-free survival (PFS) and overall survival (OS) versus capecitabine plus lapatinib (control) in previously treated human epidermal growth factor receptor 2-positive advanced breast cancer. Using EMILIA data, we evaluated the T-DM1 exposure-response relationship. METHODS: Exposure-response relationships were examined with four exposure metrics [model-predicted and observed minimum concentration (C min) and area under the concentration-time curve from time zero to day 21 of T-DM1 at cycle 1] and multiple efficacy (OS, PFS, objective response rate) and safety (grade ≥ 3 adverse events, grade ≥ 3 thrombocytopenia, grade ≥ 3 hepatotoxicity) endpoints...
October 11, 2017: Cancer Chemotherapy and Pharmacology
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
#15
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/29016226/trajectories-of-injectable-cancer-drug-costs-after-launch-in-the-united-states
#16
Noa Gordon, Salomon M Stemmer, Dan Greenberg, Daniel A Goldstein
Purpose Cancer drug prices at launch have increased in recent years. It is unclear how individual drug prices change over time after launch and what market determinants influence these changes. We measured the price trajectories of a cohort of cancer drugs after their launch into the US market and assessed the influence of market structure on price changes. Methods We studied the changes in mean monthly costs for a cohort of 24 patented, injectable anticancer drugs that were approved by the US Food and Drug Administration between 1996 and 2012...
October 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28986743/monosomy-17-in-potentially-curable-her2-amplified-breast-cancer-prognostic-and-predictive-impact
#17
David B Page, Hannah Wen, Edi Brogi, Dana Dure, Dara Ross, Kateri J Spinelli, Sujata Patil, Larry Norton, Clifford Hudis, Heather L McArthur
PURPOSE: HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment...
October 6, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28985927/association-between-targeted-her-2-therapy-and-breast-reconstruction-outcomes-a%C3%A2-propensity-score-matched-analysis
#18
Ronnie L Shammas, Eugenia H Cho, Adam D Glener, Luke P Poveromo, Lily R Mundy, Rachel A Greenup, Kimberly L Blackwell, Scott T Hollenbeck
BACKGROUND: Current treatment for HER-2+ breast cancer includes chemotherapy and targeted HER-2 therapy with trastuzumab and/or pertuzumab. Evidence is lacking on the safety of breast reconstructive operations in these patients. We hypothesized that targeted HER-2 therapy was not associated with post-mastectomy reconstructive outcomes. STUDY DESIGN: Women receiving chemotherapy and post-mastectomy reconstruction at Duke University Medical Center from 2006 to 2016 were retrospectively identified...
September 26, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28984651/new-anti-her2-agents-from-second-generation-tyrosine-kinases-inhibitors-to-bifunctional-antibodies
#19
Joseph Gligorov, Sandrine Richard, Vladimir Todorovic
PURPOSE OF REVIEW: HER2-positive breast cancers have benefited since the end of the twentieth century, not only from the improvement of biological knowledge, but also from major technological advances. The latter allowed the synthesis of the first generation of enzymatic inhibitors of the HER receptor family such as lapatinib, but above all, monoclonal antibodies such as trastuzumab or pertuzumab having profoundly modified the management of these cancers. However, despite outstanding progresses, there are still patients who are not cured with these first-generation treatments, and they will need new approaches to improve disease control and impact patients' survival...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28984296/male-breast-cancer-correlation-between-immunohistochemical-subtyping-and-pam50-intrinsic-subtypes-and-the-subsequent-clinical-outcomes
#20
Alfonso Sánchez-Muñoz, Luis Vicioso, Angela Santonja, Martina Álvarez, Yéssica Plata-Fernández, José Miramón, Irene Zarcos, César L Ramírez-Tortosa, Julio Montes-Torres, José M Jerez, Vanessa de Luque, Casilda Llácer, Cristina E Fernández-De Sousa, Lidia Pérez-Villa, Emilio Alba
Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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