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https://www.readbyqxmd.com/read/28102883/exploring-prognostic-factors-for-her2-positive-metastatic-breast-cancer-a-retrospective-cohort-study-in-a-major-swiss-hospital
#1
Lilian Bringolf, Bernhard Pestalozzi, Daniel Fink, Konstantin Dedes
BACKGROUND: Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment. PATIENTS AND METHODS: This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81)...
January 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28102081/deep-coverage-of-global-protein-expression-and-phosphorylation-in-breast-tumor-cell-lines-using-tmt-10-plex-isobaric-labeling
#2
Fang-Ke Huang, Guoan Zhang, Kevin Lawlor, Arpi Nazarian, John Philip, Paul Tempst, Noah Dephoure, Thomas A Neubert
Labeling peptides with isobaric tags is a popular strategy in quantitative bottom-up proteomics. In this study, we labeled six breast tumor cell lysates (1.34 mg proteins per channel) using 10-plex tandem mass tag reagents and analyzed the samples on a Q Exactive HF Quadrupole-Orbitrap mass spectrometer. We identified a total of 8706 proteins and 28186 phosphopeptides, including 7394 proteins and 23739 phosphosites common to all channels. The majority of technical replicates correlated with a R2 ≥ 0.98, indicating minimum variability was introduced after labeling...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#3
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101678/breast-carcinoma-subtypes-show-different-patterns-of-metastatic-behavior
#4
István Artúr Molnár, Béla Ákos Molnár, Laura Vízkeleti, Krisztina Fekete, Judit Tamás, Péter Deák, Csilla Szundi, Borbála Székely, Judit Moldvay, Stefan Vári-Kakas, Marcell A Szász, Balázs Ács, Janina Kulka, Anna-Mária Tőkés
The aim of our retrospective study was to analyze patterns of subtype specific metastatic spread and to identify the time course of distant metastases. A consecutive series of 490 patients with breast cancer who underwent surgery and postoperative treatment at Semmelweis University, Hungary, and diagnosed between the years 2000 and 2007 was identified from the archives of the 2nd Department of Pathology, Hungary. Molecular subtypes were defined based on the 2011 St. Gallen recommendations. Statistical analysis was performed with SPSS Statistics for Windows, Version 22...
January 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28101202/cadherin-11-expression-is-upregulated-in-invasive-human-breast-cancer
#5
Kamil Pohlodek, Yen Y Tan, Christian F Singer, Daphne Gschwantler-Kaulich
Loss of expression of cadherin-11 protein is correlated with a loss of epithelial phenotype and a gain in tumor cell proliferation and invasion. It has been hypothesized that cadherin-11 may be a molecular marker for a more aggressive subtype of breast cancer. The present study examined the expression of the mesenchymal gene/protein cadherin-11 in malignant, benign and healthy breast cancer samples. A paraffin-embedded tissue microarray of both malignant and benign/healthy breast tumor was used. Clinicopathological parameters, including age, grading, tumor size, hormone receptors and HER2 receptors status were obtained from patient medical records...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#6
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28100469/immunohistochemical-phenotype-of-breast-cancer-during-25-year-follow-up-of-the-royal-marsden-tamoxifen-prevention-trial
#7
Simone Detre, Susan Ashley, Kabir Mohammed, Ian E Smith, Trevor Powles, Mitch Dowsett
Background The randomized double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. 2471 eligible participants were randomly assigned to tamoxifen (20mg/day) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of ER-positive invasive breast cancer mostly in the post treatment period. Biomarker analysis in this population may identify any sub-group specific preventive effects tamoxifen. Methods After a median follow-up of 18...
January 18, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28099938/bi-rads-3-5-microcalcifications-can-preoperatively-predict-breast-cancer-her2-and-luminal-a-molecular-subtype
#8
DongZhi Cen, Li Xu, Ningna Li, Zhiguang Chen, Lu Wang, Shuqin Zhou, Biao Xu, Chun Ling Liu, Zaiyi Liu, Tingting Luo
PURPOSE: To investigate associations between breast cancer molecular subtype and the patterns of mammographically detected calcifications. RESULTS: Identified were 93 (19.1%) Luminal A, 242 (49.9%) Luminal B, 108 (22.2%) HER2 and 42 (8.7%) basal subtypes. In univariate analysis, the clinicopathological parameters and BI-RADS 3-5 microcalcifications, which consisted 9 selected features was significantly associated with breast cancer molecular subtype (all P < 0...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099174/discordance-rate-in-estrogen-receptor-progesterone-receptor-her2-status-and-ki67-index-between-primary-unifocal-and-multiple-homogenous-breast-carcinomas-and-synchronous-axillary-lymph-node-metastases-have-an-impact-on-therapeutic-decision
#9
Rares Georgescu, Monica Boros, Denisa Moncea, Orsolya Bauer, Marius-Florin Coros, Adela Oprea, Cosmin Moldovan, Cristian Podoleanu, Simona Stolnicu
BACKGROUND: We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions. MATERIALS AND METHODS: We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases...
January 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28098887/mirna%C3%A2-375-regulates-the-cell-survival-and-apoptosis-of-human-non%C3%A2-small-cell-carcinoma-by-targeting-her2
#10
Longqiang Cheng, Bingxiang Zhan, Peng Luo, Baolong Wang
micro (mi)‑RNAs are a class of small non‑coding RNAs that regulate gene expression by binding to the 3'‑untranslated region of mRNA, which may lead to mRNA degradation or transcription regulation. Previous studies indicated that miRNAs are important for the pathogenesis of human cancer. miR‑375 has been implicated in various tumor types; however, the biological activity in human non‑small cell lung carcinoma (NSCLC) cells remains to be fully elucidated. The purpose of the present study was to investigate the biological importance of miR‑375 in human NSCLC cells...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098572/metastatic-organotropism-an-intrinsic-property-of-breast-cancer-molecular-subtypes
#11
Shi Wei, Gene P Siegal
It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone...
January 16, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28098202/superresolution-imaging-of-clinical-formalin-fixed-paraffin-embedded-breast-cancer-with-single-molecule-localization-microscopy
#12
Matthew K Creech, Jing Wang, Xiaolin Nan, Summer L Gibbs
Millions of archived formalin-fixed, paraffin-embedded (FFPE) specimens contain valuable molecular insight into healthy and diseased states persevered in their native ultrastructure. To diagnose and treat diseases in tissue on the nanoscopic scale, pathology traditionally employs electron microscopy (EM), but this platform has significant limitations including cost and painstaking sample preparation. The invention of single molecule localization microscopy (SMLM) optically overcame the diffraction limit of light to resolve fluorescently labeled molecules on the nanoscale, leading to many exciting biological discoveries...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#13
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina F A S Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression toward aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, p53 mutation frequency exceeds 50% in Triple Negative BC (TNBC). Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28097440/prevalence-of-nras-pten-and-akt1-gene-mutations-in-the-central-nervous-system-metastases-of-non-small-cell-lung-cancer
#14
Marcin Nicoś, Paweł Krawczyk, Bożena Jarosz, Marek Sawicki, Tomasz Trojanowski, Janusz Milanowski
Somatic mutations in NRAS, PTEN and AKT1 genes are rarely (~1%) reported in primary NSCLC, but their role in carcinogenesis have been proven. Therefore, we assessed the frequency of them in 145 FFPE tissue samples from CNS metastases of NSCLC using the real-time PCR technique. We identified four (two NRAS and single AKT1 and PTEN) mutations in CNS metastases of NSCLC. All mutations were observed in current male smokers (4% out of the male group; 4/100 and 4.25% out of smokers; 4/94). Three mutations have been detected in patients with SqCC (10...
January 17, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28095342/orthognathic-surgery-during-breast-cancer-treatment-a-case-report
#15
Tsuyoshi Shimo, Norie Yoshioka, Masahiro Nakamura, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Masanori Masui, Mayumi Yao, Koji Kishimoto, Shoko Yoshida, Akiyoshi Nishiyama, Hiroshi Kamioka, Akira Sasaki
INTRODUCTION: In recent years, patients with orthognathic surgery in middle-aged and elderly people have come to be a more frequent occurrence. Breast cancer is the most frequently diagnosed cancer in woman worldwide, and its prevalence rate is steadily increasing. PRESENTATION OF CASE: We report a case of a 47-year-old Japanese woman in whom left-side breast cancer (Stage 1) was unexpectedly found just before orthognathic surgery in April 2012. Breast-conserving surgery was performed (estrogen receptor+, progesterone receptor+, HER2 -, surgical margin+, sentinel lymph node +) that May...
January 3, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28094573/advanced-gastric-adenocarcinoma-optimizing-therapy-options
#16
Dilsa Mizrak Kaya, Kazuto Harada, Yusuke Shimodaira, Fatemeh G Amlashi, Quan Lin, Jaffer A Ajani
Gastric adenocarcinoma (GAC) is the fifth most common cancer and third leading cause of cancer related mortality worldwide. When localized, cure is achievable with surgery and adjunctive therapies in some patients, however, once advanced, GAC is not a curable condition. Only two targeted agents (trastuzumab and ramucirumab) have been approved and apatinib was approved only in China. Because of the heterogeneous nature of GAC, it is not possible to assess a standard therapeutic approach. Areas Covered: In this review, we aimed to describe the optimal systemic therapy regimens for advanced GAC...
January 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28092860/design-synthesis-and-biological-evaluation-of-quinazoline-phosphoramidate-mustard-conjugates-as-anticancer-drugs
#17
Songwen Lin, Yingbo Li, Yufen Zheng, Laichun Luo, Qi Sun, Zemei Ge, Tieming Cheng, Runtao Li
A series of novel compounds with phosphoramide mustard functionality incorporated into the quinazoline scaffold of EGFR/HER2 inhibitors were designed and synthesized as multi-target-directed ligands against tumor cells. In vitro assays showed that tumor cell lines with high HER2 level were more sensitive to the compounds than tumor cells with low HER2 level. Compound 10d (EMB-3) was one of the most potent inhibitors with IC50 of 7.4 nM and 82 nM against EGFR and HER2, respectively. The mechanism studies were also supported by the effect of 10d-induced DNA damage in MDA-MB-468 cells...
January 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28092723/pertuzumab-and-breast-cancer-another-piece-in-the-anti-her2-puzzle
#18
Dr Lorenzo Gerratana, Dr Marta Bonotto, Dr Claudia Bozza, Dr Elena Ongaro, Dr Valentina Fanotto, Dr Giacomo Pelizzari, Prof Fabio Puglisi
The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On June 8, 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint. Areas covered: The review provides insights into the main mechanisms of action of pertuzumab...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28090417/pattern-of-local-recurrence-and-distant-metastasis-in-breast-cancer-by-molecular-subtype
#19
Xingrao Wu, Ayesha Baig, Goulnar Kasymjanova, Kamran Kafi, Christina Holcroft, Hind Mekouar, Annie Carbonneau, Boris Bahoric, Khalil Sultanem, Thierry Muanza
BACKGROUND AND PURPOSE:  No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting...
December 9, 2016: Curēus
https://www.readbyqxmd.com/read/28089784/axillary-management-of-stage-ii-iii-breast-cancer-patients-treated-with-neoadjuvant-systemic-therapy-results-of-calgb-40601-her2-positive-and-calgb-40603-triple-negative
#20
David W Ollila, Constance T Cirrincione, Donald A Berry, Lisa A Carey, William M Sikov, Clifford A Hudis, Eric P Winer, Mehra Golshan
OBJECTIVES: Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from two NST trials: HER2-positive (CALGB40601) and triple-negative (CALGB40603). METHODS: Axillary evaluation pre-/post-NST was per the treating surgeon and could include sentinel node biopsy (SNB). Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND)...
January 12, 2017: Journal of the American College of Surgeons
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