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Metastatic Breast

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https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#1
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27926932/epsin-family-member-3-and-ribosome-related-genes-are-associated-with-late-metastasis-in-estrogen-receptor-positive-breast-cancer-and-long-term-survival-in-non-small-cell-lung-cancer-using-a-genome-wide-identification-and-validation-strategy
#2
Birte Hellwig, Katrin Madjar, Karolina Edlund, Rosemarie Marchan, Cristina Cadenas, Anne-Sophie Heimes, Katrin Almstedt, Antje Lebrecht, Isabel Sicking, Marco J Battista, Patrick Micke, Marcus Schmidt, Jan G Hengstler, Jörg Rahnenführer
BACKGROUND: In breast cancer, gene signatures that predict the risk of metastasis after surgical tumor resection are mainly indicative of early events. The purpose of this study was to identify genes linked to metastatic recurrence more than three years after surgery. METHODS: Affymetrix HG U133A and Plus 2.0 array datasets with information on metastasis-free, disease-free or overall survival were accessed via public repositories. Time restricted Cox regression models were used to identify genes associated with metastasis during or after the first three years post-surgery (early- and late-type genes)...
2016: PloS One
https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#3
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926494/p38-and-jnk-pathways-control-e-selectin-dependent-extravasation-of-colon-cancer-cells-by-modulating-mir-31-transcription
#4
Liang Zhong, Bryan Simoneau, Jacques Huot, Martin J Simard
Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to vascular endothelial cells. It requires the interaction between adhesion receptors such as E-selectin present on endothelial cells and their ligands on cancer cells. Notably, E-selectin influences the metastatic potential of breast, bladder, gastric, pancreatic, and colorectal carcinoma as well as of leukemia and lymphoma. Here, we show that E-selectin expression induced by the pro-inflammatory cytokine IL-1β is directly and negatively regulated by miR-31...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925039/metaplastic-squamous-cell-carcinoma-of-the-breast-a-case-report-and-literature-review
#5
Luciana Graziano, Paschoal Graziano, Almir Galvão Vieira Bitencourt, Daniel Bernal Soto, Alexandre Hiro, Cíntia Camillo Nunes
Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this type of lesion in the breast is uncertain. The most common sources of metastatic squamous cell carcinoma of the breast are lung, esophagus, cervix, and urinary bladder. Squamous cell carcinomas may present clinically with inflammation and average size greater than breast adenocarcinoma. As for imaging studies, mammography shows no typical findings and ultrasound can show a complicated cyst or an inflammatory process, among the differential diagnoses...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27924154/early-diagnosis-of-brain-metastases-using-a-biofluids-metabolomics-approach-in-mice
#6
James R Larkin, Alex M Dickens, Timothy D W Claridge, Claire Bristow, Kleopatra Andreou, Daniel C Anthony, Nicola R Sibson
Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown. Metastatic mammary carcinoma cells (4T1-GFP) were injected into BALB/c mice via intracerebral, intracardiac or intravenous routes to induce differing cerebral and systemic tumour burdens. B16F10 melanoma and MDA231BR-GFP human breast carcinoma cells were used for additional modelling...
2016: Theranostics
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#7
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923036/cotargeting-of-cyp-19-aromatase-and-emerging-pivotal-signalling-pathways-in-metastatic-breast-cancer
#8
REVIEW
Stine Daldorff, Randi Margit Ruud Mathiesen, Olav Erich Yri, Hilde Presterud Ødegård, Jürgen Geisler
Aromatase inhibition is one of the cornerstones of modern endocrine therapy of oestrogen receptor-positive (ER+) metastatic breast cancer (MBC). The nonsteroidal aromatase inhibitors anastrozole and letrozole, as well as the steroidal aromatase inactivator exemestane, are the preferred drugs and established worldwide in all clinical phases of the disease. However, although many patients suffering from MBC experience an initial stabilisation of their metastatic burden, drug resistance and disease progression occur frequently, following in general only a few months on treatment...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27922686/necrox-5-prevents-breast-cancer-metastasis-by-akt-inhibition-via-reducing-intracellular-calcium-levels
#9
Jin-Hee Park, Hyoung Kyu Kim, Hana Jung, Ki Hyang Kim, Mi Seon Kang, Jun Hyuk Hong, Byeng Chul Yu, Sungjae Park, Su-Kil Seo, Il Whan Choi, Soon Ha Kim, Nari Kim, Jin Han, Sae Gwang Park
A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent...
December 5, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27920693/capecitabine-induced-coronary-vasospasm
#10
Danish Henry, Francine Rudzik, Allison Butts, Aju Mathew
Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is approved for early-stage and advanced colorectal cancer and metastatic breast cancer. Cardiotoxicity of 5-FU is well described in the literature. However, cardiac adverse effects of capecitabine are poorly described. We report a case of coronary vasospasm induced by capecitabine. A 41-year-old female with metastatic breast cancer presented with chest pain 3 days after starting capecitabine. The chest pain was relieved by rest and exacerbated by exertion...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920688/complete-and-sustained-response-with-a-doublet-chemotherapy-protocol-in-an-81-year-old-patient-with-metastatic-breast-cancer
#11
Taynah Cascaes Puty, Gabriel S A Brito, Mariana S Dias, Henrique C Miranda, Juliana R Chaves, Heryvelton L Freitas, Luís E W Carvalho
Metastatic breast cancer (MBC) entails an overall 5-year survival of approximately 25%. The choice of therapy is influenced by expression of the HER2 gene and hormone receptors, by a disease-free interval, and by age. The use of paclitaxel combined with gemcitabine (doublet protocol) has shown efficacy as first-line treatment for MBC in either initial or maintenance therapy when compared to monotherapy with paclitaxel. There is evidence showing that the doublet protocol is a good alternative to maintenance therapy in women under 50 years old...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920629/electrochemotherapy-in-the-treatment-of-massive-multisite-breast-cancer-metastasis-to-the-skin-and-subcutaneous-tissue-a-case-report
#12
Mateusz Wichtowski, Paweł Potocki, Joanna Kufel-Grabowska, Joanna Streb, Dawid Murawa
BACKGROUND: Chest wall recurrence (CWR) from breast cancer after mastectomy is a difficult to treat disease. Electrochemotherapy (ECT) provides a safe, efficient, and non-invasive locoregional treatment approach in this setting. CASE REPORT: A 61-year-old woman presented with unresectable breast cancer recurrence to the skin and subcutaneous tissue for which numerous lines of treatment were unsuccessful. Between February 2015 and May 2015, the patient underwent 3 courses of ECT after which a spectacular regression of the cutaneous metastatic foci was observed...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27920001/a-case-report-of-pneumocystis-jiroveci-pneumonia-in-a-patient-with-metastatic-breast-cancer
#13
Abhijit Ray, Brian Khong, Hung T Khong
We describe a 69-year-old woman with metastatic breast cancer who developed dyspnea on exertion, persistent cough, fever and fatigue while on everolimus and exemestane combination. The initial differentials included opportunistic infection such as pneumocystis jiroveci pneumonia (PJP) vs. pneumonitis. Bronchoalveolar lavage (BAL) from bronchoscopy revealed PJP. The patient recovered after appropriate treatment. We also correlated the progressive decrease in her absolute lymphocyte count with PJP infection and recovery...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919976/phase-i-study-of-triweekly-nab-paclitaxel-combined-with-s-1-in-patients-with-her2-negative-metastatic-breast-cancer
#14
Koichi Sakaguchi, Katsuhiko Nakatsukasa, Tetsuya Taguchi
AIM: We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). PATIENTS AND METHODS: This study was carried out with a 3+3 dose escalation design; patients with HER2-negative MBC received nab-paclitaxel at 180-260 mg/m(2) on day 1 and S-1 at 65-80 mg/m(2) daily on days 1-14, repeated every 3 weeks...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919965/bevacizumab-combined-with-docetaxel-or-paclitaxel-as-first-line-treatment-of-her2-negative-metastatic-breast-cancer
#15
Leena Tiainen, Minna Tanner, Outi Lahdenperä, Pia Vihinen, Arja Jukkola, Peeter Karihtala, Niina Paunu, Teppo Huttunen, Pirkko-Liisa Kellokumpu-Lehtinen
AIM: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. PATIENTS AND METHODS: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m(2) docetaxel (days 1 and 15, q4w) or 90 mg/m(2) paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919946/in-vivo-selection-of-intermediately-and-highly-malignant-variants-of-triple-negative-breast-cancer-in-orthotopic-nude-mouse-models
#16
Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M Hoffman
AIM: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MATERIALS AND METHODS: MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×10(7) cells/site) were initially injected subcutaneously in the flank of nude mice...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919267/targeted-drug-delivery-of-near-ir-fluorescent-doxorubicin-conjugated-poly-ethylene-glycol-bisphosphonate-nanoparticles-for-diagnosis-and-therapy-of-primary-and-metastatic-bone-cancer-in-a-mouse-model
#17
S Rudnick-Glick, E Corem-Salkmon, I Grinberg, S Margel
BACKGROUND: Most primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca(2+) ions and are widely used in the treatment of bone disorders. RESULTS: We have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e...
December 5, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27918780/effect-of-a-proposed-trastuzumab-biosimilar-compared-with-trastuzumab-on-overall-response-rate-in-patients-with-erbb2-her2-positive-metastatic-breast-cancer-a-randomized-clinical-trial
#18
Hope S Rugo, Abhijit Barve, Cornelius F Waller, Miguel Hernandez-Bronchud, Jay Herson, Jinyu Yuan, Rajiv Sharma, Mark Baczkowski, Mudgal Kothekar, Subramanian Loganathan, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D Parra, Maria Luisa T Abesamis-Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Mamillapalli, Sirshendu Ray, Eduardo P Yanez Ruiz, Eduardo Pennella
Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer...
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27918726/marianne-impact-on-current-treatment-of-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-and-implications-for-the-future
#19
Komal Jhaveri
No abstract text is available yet for this article.
November 14, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27918549/a-hypoxia-responsive-traf6-atm-h2ax-signalling-axis-promotes-hif1%C3%AE-activation-tumorigenesis-and%C3%A2-metastasis
#20
Abdol-Hossein Rezaeian, Chien-Feng Li, Ching-Yuan Wu, Xian Zhang, Jorge Delacerda, M James You, Fei Han, Zhen Cai, Yun Seong Jeong, Guoxiang Jin, Liem Phan, Ping-Chieh Chou, Mong-Hong Lee, Mien-Chie Hung, Dos Sarbassov, Hui-Kuan Lin
The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in order to allow successful VHL-independent HIF1α transcriptional activation. We show that mono-ubiquitylation and phosphorylation of H2AX, which are strictly mediated by hypoxia-induced E3 ligase activity of TRAF6 and ATM, critically regulate HIF1α-driven tumorigenesis...
December 5, 2016: Nature Cell Biology
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