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Her2 positive breast cancer

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https://www.readbyqxmd.com/read/28747748/the-epigenetic-landscape-of-promoter-genome-wide-analysis-in-breast-cancer
#1
Seher Karsli-Ceppioglu, Aslihan Dagdemir, Gaëlle Judes, André Lebert, Frédérique Penault-Llorca, Yves-Jean Bignon, Dominique Bernard-Gallon
Breast cancer is a heterogeneous disease due to its clinico-pathological features and response to therapy. The classification of breast tumors based on their hormone receptor status and pathologic features. Post-translational histone modifications come into prominence for regulation of gene expression in cancer pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and matched normal tissue samples. Breast cancer tumors were classified according to St Gallen Consensus 2013...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746978/digital-image-analysis-of-her2-immunohistochemistry-in-gastric-and-oesophageal-adenocarcinoma-a-validation-study-on-biopsies-and-surgical-specimens
#2
Timco Koopman, Geertruida H de Bock, Henk J Buikema, Maria M Smits, Maarten Louwen, Mariska Hage, Alex Lt Imholz, Bert van der Vegt
AIMS: to test the validity of diagnostics incorporating digital image analysis (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in gastro-oesophageal adenocarcinomas, as an alternative to current standard diagnostics using manual scoring. METHODS AND RESULTS: we included 319 consecutive gastro-oesophageal adenocarcinomas (232 biopsies and 87 surgical specimens). DIA was applied to determine HER2 IHC classification, using both standard breast cancer (BC) and modified gastro-oesophageal cancer (GEC) cutoffs...
July 26, 2017: Histopathology
https://www.readbyqxmd.com/read/28745321/conditional-expression-of-ki-ras-g12v-in-the-mammary-epithelium-of-transgenic-mice-induces-estrogen-receptor-alpha-er%C3%AE-positive-adenocarcinoma
#3
S Andò, R Malivindi, S Catalano, P Rizza, I Barone, S Panza, D Rovito, C Emprou, J-M Bornert, G Laverny, D Metzger
Appropriate 'in vivo' models are crucial for studying breast cancer biology and evaluating the efficacy of therapeutic agents. Thus we engineered a novel transgenic mouse line expressing the human Ki-Ras bearing an activating mutation (Ki-Ras((G12V))) selectively in the mammary epithelium after lactation. These mice develop invasive ductal adenocarcinomas with 100% incidence within 3-9 months after Ki-Ras((G12V)) induction. Immunophenotyping revealed that the mammary tumors express luminal markers, are positive for estrogen and progesterone receptors, negative for HER2 and have a low proliferation index...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28743832/a-nomogram-to-predict-her2-status-in-breast-cancer-patients-with-her2-borderline-disease-as-determined-via-immunohistochemistry
#4
Qianqian Guo, Kai Chen, Xiaojie Lin, Yi Su, Rui Xu, Yan Dai, Chang Qiu, Xue Song, Siying Mao, Qianjun Chen
This study aimed to develop a nomogram to predict fluorescence in situ hybridization (FISH) assay results for HER2-borderline breast cancer as determined via immunohistochemistry (IHC) among patients in China. We reviewed a database of breast cancer patients diagnosed between January 2007 and April 2013 at our institutions. We used logistic regression to develop a nomogram and we used receiver operating characteristic curve analysis and calibration plots to validate our nomogram. In total, 1138, 301 and 344 patients had IHC-determined HER2-negative, HER2-borderline and HER2-positive disease, respectively...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28741274/cyclin-dependent-kinase-4-6-inhibitors-in-breast-cancer-palbociclib-ribociclib-and-abemaciclib
#5
REVIEW
Dorota Kwapisz
PURPOSE: The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression and its dysregulation is an important contributor to endocrine therapy resistance. CDK4/6 inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising results of efficacy and manageable safety profiles. The main objective of this review is to discuss preclinical and clinical data to date, and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in breast cancer...
July 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28739757/multifocal-and-multicentric-breast-carcinoma-a-significantly-more-aggressive-tumor-than-unifocal-breast-cancer
#6
Zhiqiang Lang, Yanqiu Wu, Cuiyan Li, Xinna Li, Xuan Wang, Guimei Qu
BACKGROUND/AIM: There are still many questions that surround multifocal or multicentric breast carcinoma (MMBC). The aim of this study was to analyze the clinicopathological characteristics of MMBC and provide feasible suggestions for therapy. PATIENTS AND METHODS: A total of 156 cases of MMBC in 3,597 invasive ductal breast carcinomas were collected and reviewed. Some factors related with prognosis such as tumor size, lymph node metastasis and others were assessed in each tumor focus, and mismatches among foci were recorded...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739750/impact-of-a-21-gene-recurrence-score-test-on-the-choice-of-adjuvant-chemotherapy-for-hormone-receptor-positive-early-stage-breast-cancer-a-prospective-study
#7
Yinduo Zeng, Qian Li, Tao Qin, Shunrong Li, Liang Jin, Jiannan Wu, Kai Chen, Heran Deng, Nanyan Rao, Qiang Liu, Fengxi Su, Weijuan Jia, Herui Yao
BACKGROUND: Studies have recommended a 21-gene recurrence score (RS) to optimize adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone receptor-positive (HR(+)) and human epidermal growth factor receptor-2 negative (HER2(-)) tumors. This study aimed to prospectively evaluate the impact of this RS in Chinese patients with breast cancer. PATIENTS AND METHODS: We prospectively collected 227 patients with EBC with estrogen receptor-positive (ER(+)) and HER2(-) tumors...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739739/transcriptional-profiling-of-sonic-hedgehog-in-a-prospective-cohort-of-breast-cancer-in-a-pakistani-population
#8
Syeda Kiran Riaz, Lin Ye, Namood E Sahar, Durkhshan Aman, Javeria Qadir, Jahangir Sarwar Khan, Muhammad Saeed, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND/AIM: Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored. MATERIALS AND METHODS: qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed. RESULTS: A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28737130/effect-of-pertuzumab-trastuzumab-and-docetaxel-in-her2-positive-metastatic-breast-cancer-a-meta-analysis%C3%A2
#9
Tian Tian, Jing Ye, Sihai Zhou
INTRODUCTION: Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pertuzumab supplementation in patients with HER2-positive metastatic breast cancer. METHODS: Medline, SCOPUS, Google Scholar, Cochrane library databases, EMBASE, Springer, and Science Direct were systematically searched...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28735068/primary-metastatic-breast-cancer-in-the-era-of-targeted-therapy-prognostic-impact-and-the-role-of-breast-tumour-surgery
#10
Jana Barinoff, Marcus Schmidt, Andreas Schneeweiss, Winfried Schoenegg, Marc Thill, Stella Keitel, Claus R Lattrich, Axel Hinke, Andreas Kutscheidt, Christian Jackisch
BACKGROUND: Except for meeting the individual palliative need, the benefit of breast surgery in primary metastatic breast cancer (PMBC), also known as de novo metastatic breast cancer, on long-term outcomes remains controversial. Twenty-four hundred and one patients with metastatic breast cancer, enrolled between 2000 and 2011 in two prospective non-interventional studies on targeted therapy, were screened with respect to this question. METHODS: One study investigated trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in addition to mainly first-line chemotherapy...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28733983/population-pharmacokinetics-and-exposure-response-of-trastuzumab-emtansine-in-advanced-breast-cancer-previously-treated-with-%C3%A2-2-her2-targeted-regimens
#11
Shang-Chiung Chen, Angelica Quartino, Daniel Polhamus, Matthew Riggs, Jonathan French, Xin Wang, Shweta Vadhavkar, Melanie Smitt, Silke Hoersch, Alexander Strasak, Jin Yan Jin, Sandhya Girish, Chunze Li
AIMS: We conducted population pharmacokinetic (PopPK) and exposure-response analyses for trastuzumab emtansine (T-DM1) to assess the need for T-DM1 dose optimization in patients with low exposure by using TH3RESA study data (NCT01419197). The randomized phase III TH3RESA study investigated T-DM1 vs. treatment of physician's choice (TPC) in patients with heavily pretreated HER2-positive advanced breast cancer. METHODS: We compared a historical T-DM1 PopPK model with T-DM1 pharmacokinetics in TH3RESA and performed exposure-response analyses using model-predicted cycle 1 Cmax , cycle 1 Cmin , and AUCss ...
July 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#12
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28730768/modulatory-effect-of-neoadjuvant-chemotherapy-on-the-prognosis-of-patients-with-breast-cancer
#13
Jasna Trifunovic, Numa Memisevic, Borislava Nikolin, Svetlana Salma, Tihomir Dugandzija, Vladimir Vidovic
PURPOSE: To evaluate the changes in biological markers ER, PR, HER2 and Ki67 in residual tumor after surgery for locally advanced breast cancer (LABC), and also to evaluate the outcome of breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: 144 breast cancer patients treated with NAC at the Oncology Institute of Vojvodina, Serbia from 2011 to 2015 were included in this study. Changes in biologic markers ER,PR, HER2/neu and Ki-67 were evaluated at diagnostic core biopsy and at the final surgery tissue specimens...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28727815/polymorphisms-associated-with-everolimus-pharmacokinetics-toxicity-and-survival-in-metastatic-breast-cancer
#14
Tomas Pascual, María Apellániz-Ruiz, Cristina Pernaut, Cecilia Cueto-Felgueroso, Pablo Villalba, Carlos Álvarez, Luis Manso, Lucia Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona, Eva Ciruelos
PURPOSE: Metastatic breast cancer (MBC) progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS) compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs) on outcomes from this treatment through a pharmacogenetic analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#15
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725277/sabcs-2016-systemic-therapy-for-metastatic-breast-cancer
#16
REVIEW
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Richard Greil
At the 2016 San Antonio Breast Cancer Symposium, several interesting phase II and phase III studies investigating systemic therapies for metastatic breast cancer were presented. The PrEGOC 0102 trial demonstrated that the combination of fulvestrant plus everolimus is safe and effective and could be an alternative to exemestane plus everolimus for selected patients with hormone-receptor positive, HER2-negative disease. The pan-PI3K inhibitor buparlisib showed some activity in combination with fulvestrant after failure of everolimus in the BELLE-3 trial...
2017: Memo
https://www.readbyqxmd.com/read/28723628/ese-1-elf3-mrna-expression-associates-with-poor-survival-outcomes-in-her2-breast-cancer-patients-and-is-critical-for-tumorigenesis-in-her2-breast-cancer-cells
#17
Adwitiya Kar, Arthur Gutierrez-Hartmann
ESE-1/Elf3 and HER2 appear to establish a positive feedback regulatory loop, but the precise role of ESE-1 in HER2+ breast tumorigenesis remains unknown. Analyzing public repositories, we found that luminal B and HER2 subtype patients with high ESE-1 mRNA levels displayed worse relapse free survival. We stably knocked down ESE-1 in HER2+ luminal B BT474 cells and HER2 subtype SKBR3 cells, which resulted in decreased cell proliferation, colony formation, and anchorage-independent growth in vitro. Stable ESE-1 knockdown inhibited HER2-dependent signaling in BT474 cells and inhibited mTOR activation in SKBR3 cells, but reduced Akt signaling in both cell types...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721185/the-smooth-and-bumpy-road-of-trastuzumab-administration-from-intravenous-iv-in-a-hospital-to-subcutaneous-sc-at-home
#18
Waa Tjalma, M T Huizing, K Papadimitriou
Trastuzumab has become standard of care in the treatment of early and metastatic HER2-positive breast cancer. Initially trastuzumab could only be administered intravenously (IV), however since a few years there is also a subcutaneous (SC) formulation. The efficacy and the safety profile of both formulations is the comparable. The administration logistics however have an impact on the patients, the health care professionals (HCPs), the hospital and the government. The preference for the patients (89%) and the HCPs (77%) is in favour of the SC formulation...
March 2017: Facts, Views & Vision in ObGyn
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#19
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 24, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28717761/estimation-of-premature-deaths-from-lack-of-access-to-anti-her2-therapy-for-advanced-breast-cancer-in-the-brazilian-public-health-system
#20
Márcio Debiasi, Tomás Reinert, Rafael Kaliks, Gilberto Amorim, Maira Caleffi, Carlos Sampaio, Gustavo Dos Santos Fernandes, Carlos H Barrios
PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic tumors treated in the public health system in Brazil do not have access to trastuzumab. This study aimed to estimate the impact of the lack of access to anti-HER2 therapies on the mortality of these patients. METHODS: On the basis of published data, the number of patients with HER2-positive advanced breast cancer in 2016 who should receive anti-HER2 targeted therapy was estimated...
June 2017: Journal of Global Oncology
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