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https://www.readbyqxmd.com/read/28932627/addition-of-anti-estrogen-therapy-to-anti-her2-dendritic-cell-vaccination-improves-regional-nodal-immune-response-and-pathologic-complete-response-rate-in-patients-with-er-pos-her2-pos-early-breast-cancer
#1
Lea Lowenfeld, Salman Zaheer, Crystal Oechsle, Megan Fracol, Jashodeep Datta, Shuwen Xu, Elizabeth Fitzpatrick, Robert E Roses, Carla S Fisher, Elizabeth S McDonald, Paul J Zhang, Angela DeMichele, Rosemarie Mick, Gary K Koski, Brian J Czerniecki
HER2-directed therapies are less effective in patients with ER(pos) compared to ER(neg) breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2(pos)/ER(pos) early breast cancer patients. In pre-clinical studies of HER2(pos) breast cancer cell lines, ER(pos) cells were partially resistant to CD4(+) Th1 cytokine-induced metabolic suppression compared with ER(neg) cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28930829/the-curative-effects-of-radiotherapy-based-therapies-for-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-a-meta-analysis
#2
Minghai Shao, Chi Zhang, Qin Qin, Zhaoyue Zhang, Hongcheng Zhu, Xiaoke Di, Xinchen Sun
AIM: This meta-analysis was designed to fully assess the curative effects of radiotherapy-based therapies for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: English articles were retrieved through searching Cochrane library, PubMed, and Embase databases updated to February 2017. Studies were selected based on the inclusion and exclusion criteria. The curative effects of radiotherapy-based therapies forHER2+ BC patients were assessed using hazard rates (HRs) or odds ratios (ORs), as well as their 95% confidence intervals (CIs)...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28930447/ultra-sensitive-quantitation-of-plasma-membrane-proteins-via-isrta
#3
Tao Gao, Bei Wang, Liu Shi, Xiaoli Zhu, Yang Xiang, Jun-Ichi Anzai, Genxi Li
Quantitation of plasma membrane proteins (PMPs) are fundamental and frequently performed in the daily lab-work. However, challenged by inherent/interacted hetero-structures and complex surroundings of the PMPs in lipid membrane, quantitative techniques for PMP often require complex treatments (e.g. labelling, isolation, purification, and determination), and the sensitivity is usually not satisfactory. To address the problem, we have proposed a novel method that enables quantitation of PMPs with extremely high sensitivity, in an easier-to-manipulate and more streamlined way...
September 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28928834/cd55-and-cd59-expression-protects-her2-overexpressing-breast-cancer-cells-from-trastuzumab-induced-complement-dependent-cytotoxicity
#4
Yu Wang, Ya-Jun Yang, Zhu Wang, Juan Liao, Mei Liu, Xiao-Rong Zhong, Hong Zheng, Yan-Ping Wang
A large proportion (40-60%) of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer do not benefit from trastuzumab treatment, potentially due to the lack of complement-dependent cytotoxicity (CDC) activation. In the present study, the effect of complement decay-accelerating factor (CD55) and CD59 glycoprotein precursor (CD59) expression on trastuzumab-induced CDC in HER2-positive breast cancer cell lines was investigated. The CD55 and CD59-overexpressing and HER2-positive cell lines SK-BR-3 and BT474 were selected for subsequent experiments...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927692/prognostic-influence-of-tumor-stroma-on-breast-cancer-subtypes
#5
Sandra Cid, Noemi Eiro, Berta Fernández, Rosario Sánchez, Alejandro Andicoechea, Pablo Ignacio Fernández-Muñiz, Luis O González, Francisco J Vizoso
INTRODUCTION: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS: A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status)...
August 19, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28923853/adaptation-to-tki-treatment-reactivates-erk-signaling-in-tyrosine-kinase-driven-leukemias-and-other-malignancies
#6
Joshua K Bruner, Hayley S Ma, Li Li, Alice Can Ran Qin, Michelle A Rudek, Richard J Jones, Mark J Levis, Keith W Pratz, Christine A Pratilas, Donald Small
FLT3 tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia. We hypothesized that FLT3/ITD leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared to either drug alone...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923573/neoadjuvant-buparlisib-plus-trastuzumab-and-paclitaxel-for-women-with-her2-primary-breast-cancer-a-randomised-double-blind-placebo-controlled-phase-ii-trial-neophoebe
#7
Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee, Sabine Turri, Patrick Urban, Sherko Kümmel, Guenther Steger, Andrea Gombos, Michael Lux, Martine J Piccart, Gunter Von Minckwitz, José Baselga, Sherene Loi
AIM: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer. METHODS: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel...
September 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28923419/tumor-associated-macrophages-are-strongly-related-to-vascular-invasion-non-luminal-subtypes-and-interval-breast-cancer
#8
Tor A Klingen, Ying Chen, Hans Aas, Elisabeth Wik, Lars A Akslen
Tumor associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163 positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163 positive macrophages were counted in the most active areas (hot-spots) and dichotomized as high (upper quartile) and low counts...
September 15, 2017: Human Pathology
https://www.readbyqxmd.com/read/28923217/current-challenges-in-the-management-of-breast-cancer-brain-metastases
#9
REVIEW
Ciara C O'Sullivan, Nicole N Davarpanah, Jame Abraham, Susan E Bates
Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287)...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28922685/neoadjuvant-systemic-therapy-for-breast-cancer-the-westmead-experience
#10
Annelise M Cocco, David Messer, Alexander Brown, Nina Sriram, Jenny Gilchrist, Loma Al-Mansouri, Richard Kefford, Farid Meybodi, James French, Jeremy Hsu, Elisabeth Elder
BACKGROUND: Neoadjuvant systemic therapy (NAST) can be used to treat breast cancer. Pathologic complete response (pCR) is a surrogate marker for improved survival. This study examined response in the breast and axilla to NAST and identified features associated with pCR. METHODS: Patients undergoing NAST and surgery between January 2012 and June 2016 by surgeons at Westmead Breast Cancer Institute were identified. Patients with inflammatory or metastatic disease were excluded...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28922402/new-insights-into-the-metastatic-behavior-after-breast-cancer-surgery-according-to-well-established-clinicopathological-variables-and-molecular-subtypes
#11
Oreste Claudio Buonomo, Emanuele Caredda, Ilaria Portarena, Gianluca Vanni, Augusto Orlandi, Claudia Bagni, Giuseppe Petrella, Leonardo Palombi, Paolo Orsaria
Despite advances in treatment, up to 30% of patients with early breast cancer (BC) experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013). Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group). The median follow-up period among the 324 eligible patients was 7...
2017: PloS One
https://www.readbyqxmd.com/read/28919786/genetic-variants-in-long-noncoding-rna-h19-contribute-to-the-risk-of-breast-cancer-in-a-southeast-china-han-population
#12
Yuxiang Lin, Fangmeng Fu, Yazhen Chen, Wei Qiu, Songping Lin, Peidong Yang, Meng Huang, Chuan Wang
The long noncoding RNA (lncRNA) H19 is a maternally expressed imprinted gene that plays important roles in tumorigenesis, progression, and metastasis. However, the association between polymorphisms on H19 and breast cancer (BC) susceptibility has remained obscure. In this case-control study, we assessed the interaction between two lncRNA H19 single-nucleotide polymorphisms (SNPs) (rs217727 C>T, rs2839698 C>T) and the risk of BC in a Chinese Han population. In total, 1,005 BC cases and 1,020 healthy controls were enrolled in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919579/mri-and-prediction-of-pathologic-complete-response-in-the-breast-and-axilla-after-neoadjuvant-chemotherapy-for-breast-cancer-mri-and-pathologic-complete-response
#13
Joseph J Weber, Maxine S Jochelson, Anne Eaton, Emily C Zabor, Andrea V Barrio, Mary L Gemignani, Melissa Pilewskie, Kimberly J Van Zee, Monica Morrow, Mahmoud El-Tamer
BACKGROUND: In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), herein we evaluate reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes following NAC. STUDY DESIGN: Patients who had MRI before and after NAC between 06/2014-08/2015 were identified in a prospective database following IRB approval. Post NAC-MRI of the breast and axillary nodes was correlated with residual disease on final pathology...
September 14, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28919468/a-copper-based-enzyme-free-fluorescence-elisa-for-her2-detection
#14
Shiyu Tian, Ke Zeng, Aijun Yang, Qin Wang, Minghui Yang
We reported an enzyme-free ELISA to detect breast cancer biomarker human epidermal growth factor receptor 2 (HER2) in human serum samples. Instead of enzymes (such as horseradish peroxidase) used in traditional ELISA, CuO nanoparticles were utilized as the signal probe. Compared to traditional enzymes, CuO nanoparticles have the advantages of low cost and good stability. After dissolving CuO nanoparticles with acid, the Cu (II) ions generated catalyzed the reaction of o-phenylenediamine with ascorbic acid to produce fluorescent quinoxaline derivative molecules...
September 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28918577/microarray-based-snp-genotyping-to-identify-genetic-risk-factors-of-triple-negative-breast-cancer-tnbc-in-south-indian-population
#15
M Aravind Kumar, Vineeta Singh, Shaik Mohammad Naushad, Uday Shanker, M Lakshmi Narasu
In the view of aggressive nature of Triple-Negative Breast cancer (TNBC) due to the lack of receptors (ER, PR, HER2) and high incidence of drug resistance associated with it, a case-control association study was conducted to identify the contributing genetic risk factors for Triple-negative breast cancer (TNBC). A total of 30 TNBC patients and 50 age and gender-matched controls of Indian origin were screened for 9,00,000 SNP markers using microarray-based SNP genotyping approach. The initial PLINK association analysis (p < 0...
September 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28918548/tumor-and-serum-dna-methylation-in-women-receiving-preoperative-chemotherapy-with-or-without-vorinostat-in-tbcrc008
#16
Roisin M Connolly, Mary Jo Fackler, Zhe Zhang, Xian C Zhou, Matthew P Goetz, Judy C Boughey, Bridget Walsh, John T Carpenter, Anna Maria Storniolo, Stanley P Watkins, Edward W Gabrielson, Vered Stearns, Saraswati Sukumar
BACKGROUND: Methylated gene markers have shown promise in predicting breast cancer outcomes and treatment response. We evaluated whether baseline and changes in tissue and serum methylation levels would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer undergoing preoperative chemotherapy. METHODS: The TBCRC008 trial investigated pCR following 12 weeks of preoperative carboplatin and albumin-bound paclitaxel + vorinostat/placebo (n = 62)...
September 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28918115/the-interplay-of-endocrine-therapy-steroid-pathways-and-therapeutic-resistance-importance-of-androgen-in-breast-carcinoma
#17
REVIEW
Kiyoshi Takagi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified...
September 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28916978/tumor-biology-predicts-pathologic-complete-response-to-neoadjuvant-chemotherapy-in-patients-presenting-with-locally-advanced-breast-cancer
#18
Lori F Gentile, George Plitas, Emily C Zabor, Michelle Stempel, Monica Morrow, Andrea V Barrio
BACKGROUND: Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. OBJECTIVE: The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery...
September 15, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#19
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916248/breast-cancer-vaccines-delivered-by-dendritic-cell-targeted-lentivectors-induce-potent-antitumor-immune-responses-and-protect-mice-from-mammary-tumor-growth
#20
Paul D Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs...
September 12, 2017: Vaccine
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