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Metastatic her2+ breast cancer

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https://www.readbyqxmd.com/read/28938684/efficacy-and-safety-of-everolimus-in-chinese-metastatic-hr-positive-her2-negative-breast-cancer-patients-a-real-world-retrospective-study
#1
Chengcheng Gong, Yannan Zhao, Biyun Wang, Xichun Hu, Zhonghua Wang, Jian Zhang, Sheng Zhang
BACKGROUND: Everolimus combined with endocrine therapy has been proved to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). We aimed to evaluate the efficacy and safety of everolimus plus endocrine therapy in Chinese real-world practice for the first time, and investigate factors associated with efficacy. METHODS: Seventy-five HR+/HER2- MBC patients were included in this retrospective study who received everolimus plus endocrine therapy after progression on prior endocrine therapy in Fudan University Shanghai Cancer Center (FUSCC) between June 2013 and February 2016...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938164/multifunctional-superparamagnetic-nanoparticles-conjugated-with-fluorescein-labeled-designed-ankyrin-repeat-protein-as-an-efficient-her2-targeted-probe-in-breast-cancer
#2
Dong-Li Li, Jian-Er Tan, Ying Tian, Shun Huang, Peng-Hui Sun, Meng Wang, Yan-Jiang Han, Hong-Sheng Li, Hu-Bing Wu, Xing-Mei Zhang, Yi-Kai Xu, Quan-Shi Wang
Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging...
September 8, 2017: Biomaterials
https://www.readbyqxmd.com/read/28935542/phase-i-trial-of-veliparib-a-poly-adp-ribose-polymerase-inhibitor-plus-metronomic-cyclophosphamide-in-metastatic-her2-negative-breast-cancer
#3
Jesus Anampa, Alice Chen, John Wright, Margi Patel, Christine Pellegrino, Karen Fehn, Joseph A Sparano, Eleni Andreopoulou
BACKGROUND: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. METHODS: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer...
September 1, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28922685/neoadjuvant-systemic-therapy-for-breast-cancer-the-westmead-experience
#4
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
#5
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/28915642/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#6
Patrizia Vici, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D'Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria, Teresa Gamucci
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913760/impact-of-histopathology-tumor-infiltrating-lymphocytes-and-adjuvant-chemotherapy-on-prognosis-of-triple-negative-breast-cancer
#7
Roberto A Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A Gilbert, Victoria Cafourek, David W Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew P Goetz
BACKGROUND: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. METHODS: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs...
September 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28912526/mpzl1-forms-a-signalling-complex-with-grb2-adaptor-and-ptpn11-phosphatase-in-her2-positive-breast-cancer-cells
#8
Alice Beigbeder, François J M Chartier, Nicolas Bisson
HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized. We performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2+ breast cancer model to delineate GRB2-nucleated protein interaction networks...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912144/androgen-and-estrogen-receptor-imaging-in-metastatic-breast-cancer-patients-as-a-surrogate-for-tissue-biopsies
#9
Clasina M Venema, Lemonitsa H Mammatas, Carolina P Schröder, Michel van Kruchten, Giulia Apollonio, Andor W J M Glaudemans, A H H Bongaerts, Otto S Hoekstra, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F de Vries, Elisabeth G E de Vries, Ronald Boellaard, Catharina Willemien Menke-van der Houven van Oordt, Geke Ap Hospers
In addition to the well-known estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by (18)F-fluoroestradiol (FES) PET, and AR expression has been visualized in prostate cancer patients with (18)F-fluorodihydrotestosterone (FDHT) PET. Our aim was to assess the concordance between FDHT- and FES-PET and tumor AR- and ER-expression measured immunohistochemically (IHC) in patients with metastatic breast cancer...
September 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28903441/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#10
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903354/her2-isoforms-co-expression-differently-tunes-mammary-tumor-phenotypes-affecting-onset-vasculature-and-therapeutic-response
#11
Arianna Palladini, Giordano Nicoletti, Alessia Lamolinara, Massimiliano Dall'Ora, Tania Balboni, Marianna L Ianzano, Roberta Laranga, Lorena Landuzzi, Veronica Giusti, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Enrico Di Oto, Sofia Asioli, Augusto Amici, Serenella M Pupa, Carla De Giovanni, Elda Tagliabue, Manuela Iezzi, Patrizia Nanni, Pier-Luigi Lollini
Full-length HER2 oncoprotein and splice variant Delta16 are co-expressed in human breast cancer. We studied their interaction in hybrid transgenic mice bearing human full-length HER2 and Delta16 (F1 HER2/Delta16) in comparison to parental HER2 and Delta16 transgenic mice. Mammary carcinomas onset was faster in F1 HER2/Delta16 and Delta16 than in HER2 mice, however tumor growth was slower, and metastatic spread was comparable in all transgenic mice. Full-length HER2 tumors contained few large vessels or vascular lacunae, whereas Delta16 tumors presented a more regular vascularization with numerous endothelium-lined small vessels...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899363/a-phase-i-open-label-dose-escalation-study-of-the-anti-her3-monoclonal-antibody-ljm716-in-patients-with-advanced-squamous-cell-carcinoma-of-the-esophagus-or-head-and-neck-and-her2-overexpressing-breast-or-gastric-cancer
#12
Kerry Lynn Reynolds, Philippe L Bedard, Se-Hoon Lee, Chia-Chi Lin, Josep Tabernero, Maria Alsina, Ezra Cohen, José Baselga, George Blumenschein, Donna M Graham, Ignacio Garrido-Laguna, Dejan Juric, Sunil Sharma, Ravi Salgia, Abdelkader Seroutou, Xianbin Tian, Rose Fernandez, Alex Morozov, Qing Sheng, Thiruvamoor Ramkumar, Angela Zubel, Yung-Jue Bang
BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity...
September 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28895005/durable-complete-response-in-her2-positive-breast-cancer-a-multicenter-retrospective-analysis
#13
Naoki Niikura, Akihiko Shimomura, Yumi Fukatsu, Masataka Sawaki, Rin Ogiya, Hiroyuki Yasojima, Tomomi Fujisawa, Mitsugu Yamamoto, Michiko Tsuneizumi, Akira Kitani, Junichiro Watanabe, Akira Matsui, Yuko Takahashi, Seiki Takashima, Tadatoshi Shien, Kenji Tamura, Shigehira Saji, Norikazu Masuda, Yutaka Tokuda, Hhiroji Iwata
PURPOSE: Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab. METHODS: We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment...
September 11, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28892049/membrane-mucin-muc4-promotes-blood-cell-association-with-tumor-cells-and-mediates-efficient-metastasis-in-a-mouse-model-of-breast-cancer
#14
A R Rowson-Hodel, J H Wald, J Hatakeyama, W K O'Neal, J R Stonebraker, K VanderVorst, M J Saldana, A D Borowsky, C Sweeney, K L Carraway
Mucin-4 (Muc4) is a large cell surface glycoprotein implicated in the protection and lubrication of epithelial structures. Previous studies suggest that aberrantly expressed Muc4 can influence the adhesiveness, proliferation, viability and invasiveness of cultured tumor cells, as well as the growth rate and metastatic efficiency of xenografted tumors. Although it has been suggested that one of the major mechanisms by which Muc4 potentiates tumor progression is via its engagement of the ErbB2/HER2 receptor tyrosine kinase, other mechanisms exist and remain to be delineated...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28888580/predicting-brain-metastasis-in-breast-cancer-patients-stage-versus-biology
#15
Hamdy A Azim, Raafat Abdel-Malek, Loay Kassem
BACKGROUND: Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. PATIENTS AND METHODS: We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype...
August 18, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28884417/neratinib-first-global-approval
#16
Emma D Deeks
Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU...
September 7, 2017: Drugs
https://www.readbyqxmd.com/read/28882552/prognostic-and-predictive-biomarkers-in-breast-cancer-past-present-and-future
#17
REVIEW
Andrea Nicolini, Paola Ferrari, Michael J Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients...
September 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28881657/tumor-biomarker-conversion-between-primary-and-metastatic-breast-cancer-mrna-assessment-and-its-concordance-with-immunohistochemistry
#18
Stefan Stefanovic, Ralph Wirtz, Thomas M Deutsch, Andreas Hartkopf, Peter Sinn, Zsuzsanna Varga, Bettina Sobottka, Lakis Sotiris, Florin-Andrei Taran, Christoph Domschke, Andre Hennigs, Sara Y Brucker, Christof Sohn, Florian Schuetz, Andreas Schneeweiss, Markus Wallwiener
Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests. This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881584/dimerization-of-egfr-and-her2-induces-breast-cancer-cell-motility-through-stat1-dependent-acta2-induction
#19
Myeongjin Jeon, Daeun You, Soo Youn Bae, Seok Won Kim, Seok Jin Nam, Hyeon Ho Kim, Sangmin Kim, Jeong Eon Lee
The dimerization of EGFR and HER2 is associated with poor prognosis such as induction of tumor growth and cell invasion compared to when EGFR remains as a homodimer. However, the mechanism for events after dimerization in breast cancer models is not clear. We found that expressions of alpha-smooth muscle actin (ACTA2) and signal transducer and activator of transcription 1 (STAT1) significantly increased with transient or stable overexpression of HER2 in EGFR-positive breast cancer cells. ACTA2 and STAT1 expression was also increased in HER2-positive breast cancer patients...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878375/fasting-glucose-and-body-mass-index-as-predictors-of-activity-in-breast-cancer-patients-treated-with-everolimus-exemestane-the-everext-study
#20
Laura Pizzuti, Paolo Marchetti, Clara Natoli, Teresa Gamucci, Daniele Santini, Angelo Fedele Scinto, Laura Iezzi, Lucia Mentuccia, Loretta D'Onofrio, Andrea Botticelli, Luca Moscetti, Francesca Sperati, Claudio Botti, Francesca Ferranti, Simonetta Buglioni, Giuseppe Sanguineti, Simona Di Filippo, Luigi di Lauro, Domenico Sergi, Teresa Catenaro, Silverio Tomao, Antonio Giordano, Marcello Maugeri-Saccà, Maddalena Barba, Patrizia Vici
Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test...
September 6, 2017: Scientific Reports
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