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https://www.readbyqxmd.com/read/28433541/the-impact-of-2013-updated-asco-cap-her2-guidelines-on-the-diagnosis-and-management-of-invasive-breast-cancer-a-single-center-study-of-1739-cases
#1
Xiaofei Zhang, Ira Bleiweiss, Shabnam Jaffer, Anupma Nayak
BACKGROUND: The purpose of this study was to determine the impact of revised ASCO/CAP 2013 HER2 guidelines on the clinical practice of pathologists and oncologists. MATERIALS AND METHODS: Retrospective analysis of 1739 patients with invasive breast carcinoma who underwent reflex HER2 (fluorescence in situ hybridization [FISH]) testing, using both 2007 and 2013 guidelines (2007-2014). RESULTS: Using 2013 guidelines, 255 (15%; 95% confidence interval [CI], 13%-16%) cases were classified as HER2(+) as opposed to 186 (11%; 95% CI, 9%-12%) by 2007 guidelines (odds ratio [OR] 1...
March 29, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28432515/mri-predicts-pathologic-complete-response-in-her2-positive-breast-cancer-after-neoadjuvant-chemotherapy
#2
Mette S van Ramshorst, Claudette E Loo, Emilie J Groen, Gonneke H Winter-Warnars, Jelle Wesseling, Frederieke van Duijnhoven, Marie-Jeanne T Vrancken Peeters, Gabe S Sonke
BACKGROUND: Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced. METHODS: We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II-III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute...
April 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28432480/predictive-value-of-18-f-fdg-pet-ct-for-axillary-lymph-node-metastasis-in-invasive-ductal-breast-cancer
#3
Bong-Il Song, Hae Won Kim, Kyoung Sook Won
BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC). METHODS: In this study, 128 IDC patients who underwent pretreatment (18)F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed...
April 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#4
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28430631/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#5
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428285/characterisation-of-gata3-expression-in-invasive-breast-cancer-differences-in-histological-subtypes-and-immunohistochemically-defined-molecular-subtypes
#6
Tang Shaoxian, Yu Baohua, Xu Xiaoli, Cheng Yufan, Tu Xiaoyu, Lu Hongfen, Bi Rui, Sun Xiangjie, Shui Ruohong, Yang Wentao
AIMS: GATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases...
April 20, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#7
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427518/controversies-in-clinicopathological-characteristics-and-treatment-strategies-of-male-breast-cancer-a-review-of-the-literature
#8
REVIEW
Agnese Losurdo, Selene Rota, Giuseppe Gullo, Giovanna Masci, Rosalba Torrisi, Giulia Bottai, Monica Zuradelli, Wolfgang Gatzemeier, Armando Santoro
Male breast cancer (MaBC) is a rare disease, accounting for less than 1% of malignancies in men. For this reason, literature data on its clinicopathological characteristics are very heterogeneous and treatment strategies have mostly been extrapolated from the female counterpart. However, immunohistochemical peculiarities of MaBC have recently emerged, defining it as a distinct entity from female breast cancer (FBC), thus requiring a tailored clinical approach. MaBC appears to be more often hormone receptor positive than FBC, while data on HER2 status still remain inconclusive, indicating a possible higher incidence of HER2 alterations...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427429/vitamin-d-receptor-retinoid-x-receptor-and-peroxisome-proliferator-activated-receptor-%C3%AE-are-overexpressed-in-brca1-mutated-breast-cancer-and-predict-prognosis
#9
Sabine Heublein, Doris Mayr, Alfons Meindl, Alexandra Kircher, Udo Jeschke, Nina Ditsch
BACKGROUND: BRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28427196/breast-cancer-subtypes-predict-the-preferential-site-of-distant-metastases-a-seer-based-study
#10
Qi Wu, Juanjuan Li, Shan Zhu, Juan Wu, Chuang Chen, Qian Liu, Wen Wei, Yimin Zhang, Shengrong Sun
BACKGROUND AND AIMS: This study aimed to access possible relationships between breast cancer subtypes and sites of distant metastasis in breast cancer. RESULTS: A total of 243,896 patients, including 226,451 cases in control groups were identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases. Patients with all subtypes were most prone to bone metastases, the incidence of bone metastasis in HR+/HER2+ subtype was up to 5...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426845/her2-specific-chimeric-antigen-receptor-modified-virus-specific-t-cells-for-progressive-glioblastoma-a-phase-1-dose-escalation-trial
#11
Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine Robertson, Tara L Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi Grilley, Milica Stojakovic, John Hicks, Suzanne Z Powell, Malcolm K Brenner, Helen E Heslop, Robert Grossman, Winfried S Wels, Stephen Gottschalk
Importance: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. Objective: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. Design, Setting, and Participants: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28423644/disulfide-bond-disrupting-agents-activate-the-unfolded-protein-response-in-egfr-and-her2-positive-breast-tumor-cells
#12
Renan B Ferreira, Mengxiong Wang, Mary E Law, Bradley J Davis, Ashton N Bartley, Paul J Higgins, Michael S Kilberg, Katherine E Santostefano, Naohiro Terada, Coy D Heldermon, Ronald K Castellano, Brian K Law
Many breast cancer deaths result from tumors acquiring resistance to available therapies. Thus, new therapeutic agents are needed for targeting drug-resistant breast cancers. Drug-refractory breast cancers include HER2+ tumors that have acquired resistance to HER2-targeted antibodies and kinase inhibitors, and "Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#13
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423549/her2-specific-recombinant-immunotoxin-4d5scfv-pe40-passes-through-retrograde-trafficking-route-and-forces-cells-to-enter-apoptosis
#14
Evgeniya Sokolova, Evgeniy Guryev, Andrey Yudintsev, Vladimir Vodeneev, Sergey Deyev, Irina Balalaeva
Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423537/limitations-in-predicting-pam50-intrinsic-subtype-and-risk-of-relapse-score-with-ki67-in-estrogen-receptor-positive-her2-negative-breast-cancer
#15
Aranzazu Fernandez-Martinez, Tomás Pascual, Giuseppe Perrone, Serafin Morales, Juan de la Haba, Milagros González-Rivera, Patricia Galván, Francesca Zalfa, Michela Amato, Lucia Gonzalez, Miquel Prats, Federico Rojo, Luis Manso, Laia Paré, Immaculada Alonso, Joan Albanell, Ana Vivancos, Antonio González, Judit Matito, Sonia González, Pedro Fernandez, Barbara Adamo, Montserrat Muñoz, Margarita Viladot, Carme Font, Francisco Aya, Maria Vidal, Rosalía Caballero, Eva Carrasco, Vittorio Altomare, Giuseppe Tonini, Aleix Prat, Miguel Martin
PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423511/atm-kinase-sustains-breast-cancer-stem-like-cells-by-promoting-atg4c-expression-and-autophagy
#16
Martina Antonelli, Flavie Strappazzon, Ivan Arisi, Rossella Brandi, Mara D'Onofrio, Manolo Sambucci, Gwenola Manic, Ilio Vitale, Daniela Barilà, Venturina Stagni
The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423171/identification-of-patients-with-documented-pathologic-complete-response-in-the-breast-after-neoadjuvant-chemotherapy-for-omission-of-axillary-surgery
#17
Audree B Tadros, Wei T Yang, Savitri Krishnamurthy, Gaiane M Rauch, Benjamin D Smith, Vicente Valero, Dalliah M Black, Anthony Lucci, Abigail S Caudle, Sarah M DeSnyder, Mediget Teshome, Carlos H Barcenas, Makesha Miggins, Beatriz E Adrada, Tanya Moseley, Rosa F Hwang, Kelly K Hunt, Henry M Kuerer
Importance: A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective: To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design...
April 19, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28423057/insertion-of-a-ligand-to-her2-in-gb-retargets-hsv-tropism-and-obviates-the-need-for-activation-of-the-other-entry-glycoproteins
#18
Biljana Petrovic, Tatiana Gianni, Valentina Gatta, Gabriella Campadelli-Fiume
Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL and gB, activated in a cascade fashion by conformational modifications induced by cognate receptors and intermolecular signaling. The receptors are nectin1 and HVEM (Herpes virus entry mediator) for gD, and αvβ6 or αvβ8 integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#19
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28421181/mct1-in-invasive-ductal-carcinoma-monocarboxylate-metabolism-and-aggressive-breast-cancer
#20
Jennifer M Johnson, Paolo Cotzia, Roberto Fratamico, Lekha Mikkilineni, Jason Chen, Daniele Colombo, Mehri Mollaee, Diana Whitaker-Menezes, Marina Domingo-Vidal, Zhao Lin, Tingting Zhan, Madalina Tuluc, Juan Palazzo, Ruth C Birbe, Ubaldo E Martinez-Outschoorn
Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank...
2017: Frontiers in Cell and Developmental Biology
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