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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
#1
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/27920624/neoadjuvant-chemotherapy-with-docetaxel-carboplatin-and-weekly-trastuzumab-is-active-in-her2-positive-early-breast-cancer-results-after-a-median-follow-up-of-over-4-years
#2
Hans-Christian Kolberg, Leyla Akpolat-Basci, Miltiades Stephanou, Bahriye Aktas, Carla Verena Hannig, Cornelia Liedtke
INTRODUCTION: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27920432/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#3
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 2016: Scientific Reports
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
#4
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/27918782/biosimilar-therapy-for-erbb2-her2-positive-breast-cancer-close-enough
#5
Harold J Burstein, Deborah Schrag
No abstract text is available yet for this article.
December 1, 2016: JAMA: the Journal of the American Medical Association
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
#6
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/27918764/effect-of-fluorouracil-leucovorin-and-oxaliplatin-with-or-without-onartuzumab-in-her2-negative-met-positive-gastroesophageal-adenocarcinoma-the-metgastric-randomized-clinical-trial
#7
Manish A Shah, Yung-Jue Bang, Florian Lordick, Maria Alsina, Meng Chen, Stephen P Hack, Jean Marie Bruey, Dustin Smith, Ian McCaffery, David S Shames, See Phan, David Cunningham
Importance: Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC. Objective: To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC...
December 1, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27915204/powerpiinc-preoperative-window-of-endocrine-therapy-provides-information-to-increase-compliance-trial-changes-in-tumor-proliferation-index-and-quality-of-life-with-7-days-of-preoperative-tamoxifen
#8
Adam L Cohen, Rachel E Factor, Kathi Mooney, Mohamed E Salama, Mark Wade, Victoria Serpico, Emily Ostrander, Edward Nelson, Jane Porretta, Cindy Matsen, Philip Bernard, Ken Boucher, Leigh Neumayer
OBJECTIVES: A decrease in Ki67 during neoadjuvant therapy predicts response to tamoxifen. Previous trials have shown a decreased Ki67 in breast tumors with as little as two or more weeks of preoperative tamoxifen. Shortening the preoperative treatment time in window of opportunity clinical trials makes these trials more attractive to women. POWERPIINC examined the effect of 7 days of preoperative tamoxifen on breast tumor proliferation and patient symptoms. METHODS: Women with untreated stage I/II, ER-positive, invasive breast cancer with no contraindications to tamoxifen were enrolled...
December 1, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#9
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27907855/lc-ms-ms-assay-for-the-quantitation-of-the-tyrosine-kinase-inhibitor-neratinib-in-human-plasma
#10
Brian F Kiesel, Robert A Parise, Alvin Wong, Kiana Keyvanjah, Samuel Jacobs, Jan H Beumer
Neratinib is an orally available tyrosine kinase inhibitor targeting HER2 (ERBB2) and EGFR (ERBB). It is being clinically evaluated for the treatment of breast and other solid tumors types as a single agent or in combination with other chemotherapies. In support of several phase I/II clinical trials investigating neratinib combinations, we developed and validated a novel LC-MS/MS assay for the quantification of neratinib in 100μL of human plasma with a stable isotopic internal standard. Analytes were extracted from plasma using protein precipitation and evaporation of the resulting supernatant followed by resuspension...
November 22, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27905104/biomarkers-of-folate-and-vitamin-b12-and-breast-cancer-risk-report-from-the-epic-cohort
#11
M Matejcic, J de Batlle, C Ricci, C Biessy, F Perrier, I Huybrechts, E Weiderpass, Boutron-Mc Ruault, C Cadeau, M His, D G Cox, H Boeing, R T Fortner, R Kaaks, P Lagiou, A Trichopoulou, V Benetou, R Tumino, S Panico, S Sieri, D Palli, F Ricceri, H B Bueno-de-Mesquita, G Skeie, P Amiano, M J Sánchez, M D Chirlaque, A Barricarte, J R Quirós, G Buckland, C H van Gils, P H Peeters, T J Key, E Riboli, B Gylling, A Zeleniuch-Jacquotte, M J Gunter, I Romieu, V Chajès
Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27904779/generation-characterization-and-maintenance-of-trastuzumab-resistant-her2-breast-cancer-cell-lines
#12
Sandra Zazo, Paula González-Alonso, Ester Martín-Aparicio, Cristina Chamizo, Ion Cristóbal, Oriol Arpí, Ana Rovira, Joan Albanell, Pilar Eroles, Ana Lluch, Juan Madoz-Gúrpide, Federico Rojo
Trastuzumab became the therapy of choice for patients with HER2-positive breast cancer in 1998, and it has provided clinical benefit ever since. However, a significant percentage of patients show primary resistance to trastuzumab at diagnosis, and most patients with metastatic disease that initially respond to trastuzumab eventually progress (acquired resistance). Consequently, there is an urgent need to improve our knowledge of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903675/a-pam50-based-chemo-endocrine-score-for-hormone-receptor-positive-breast-cancer-with-an-intermediate-risk-of-relapse
#13
Aleix Prat, Ana Lluch, Arran K Turnbull, Anita K Dunbier, Lourdes Calvo, Joan Albanell, Juan de la Haba-Rodríguez, Angels Arcusa, Ignacio Chacón, Pedro Sánchez-Rovira, Arrate Plazaola, Montse Muñoz, Laia Paré, Joel S Parker, Nuria Ribelles, Begona Jimenez, Abdul Aziz Bin Aiderus, Rosalía Caballero, Barbara Adamo, Mitch Dowsett, Eva M Carrasco, Miguel Martín, J Michael Dixon, Charles M Perou, Emilio Alba
PURPOSE: Hormone receptor-positive (HR+) breast cancer is clinically and biologically heterogeneous and subgroups with different prognostic and treatment sensitivities need to be identified. EXPERIMENTAL DESIGN: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2- disease randomized to neoadjuvant multi-agent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based Chemo-Endocrine Score (CES)...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903634/distinct-receptor-tyrosine-kinase-subsets-mediate-anti-her2-drug-resistance-in-breast-cancer
#14
Peter B Alexander, Rui Chen, Chang Gong, Lifeng Yuan, Jeff S Jasper, Yi Ding, Geoffrey J Markowitz, Pengyuan Yang, Xin Xu, Donald P McDonnell, Erwei Song, Xiao-Fan Wang
Targeted inhibitors of the human epidermal growth factor receptor 2 (HER2) such as trastuzumab and lapatinib are among the first examples of molecularly targeted cancer therapy and have proven largely effective for the treatment of HER2-positive breast cancers. However, approximately half of those patients either do not respond to these therapies or develop secondary resistance. Although a few signaling pathways have been implicated, a comprehensive understanding of mechanisms underlying HER2 inhibitor drug resistance is still lacking...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903463/her2-transmembrane-mutations-v659-g660-that-stabilize-homo-and-hetero-dimerization-are-rare-oncogenic-drivers-in-lung-adenocarcinoma-that-respond-to-afatinib
#15
Sai-Hong Ignatius Ou, Alexa B Schrock, Eduard V Bocharov, Samuel J Klempner, Carolina Kawamura Haddad, Gary Steinecker, Melissa Johnson, Barbara J Gitlitz, Jon Chung, Paulo V Campregher, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, James H Suh, Siraj M Ali, Vamsidhar Velcheti
INTRODUCTION: HER2 transmembrane domain (TMD) mutations (HER2(V659E), HER2(G660D)) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown. METHODS: We prospectively analyzed 8,551 consecutive lung adenocarcinomas using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions. RESULTS: We identified 15 cases (0...
November 26, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27901576/the-high-frequency-of-pik3ca-mutations-in-iranian-breast-cancer-patients
#16
Ghasem Azizi Tabesh, Pantea Izadi, Forouzandeh Fereidooni, Amir Nader Emami Razavi, Javad Tavakkoly Bazzaz
In breast cancer, somatic mutations of PIK3CA oncogene are common. We investigated the mutational status of exons 9 and 20 of the PIK3CA gene by polymerase chain reaction and direct sequencing in 80 breast tumors, and observed that 45% of these contained PIK3CA mutations in the mentioned exons. These mutations were found more in progesterone receptor positive and Her2- tumors, but this association did not reach a statistically significant level. Also, we observed a significant association between PIK3CA mutations and low-grade tumors...
November 30, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27899970/fish-testing-of-her2-immunohistochemistry-1-invasive-breast-cancer-with-unfavorable-characteristics
#17
Stella Petroni, Lucia Caldarola, Rachele Scamarcio, Francesco Giotta, Agnese Latorre, Anita Mangia, Giovanni Simone
Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899774/-a-review-multigene-assays-for-clinical-utility-in-breast-cancer
#18
Kazuhiro Araki, Yoshinori Ito
Multigene assays that simultaneously measure the expression of various breast cancer genes have been developed to guide the use of adjuvant chemotherapy in early breast cancer. The efficacy of adjuvant therapies depends on the recurrence risk for an individual patient. As a result, accurate prediction of the recurrence risk is vital for precise adjuvant chemotherapy in individual breast cancer patients. The recurrence risk as typically assessed by conventional examination of histological data of immuno-histological biomarkers(ER, PR, HER2, and Ki-67)is not sufficient to select subsets of patients...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895501/a-fish-based-method-for-assessment-of-her-2-amplification-status-in-breast-cancer-circulating-tumor-cells-following-cellsearch-isolation
#19
Henrik Frithiof, Kristina Aaltonen, Lisa Rydén
INTRODUCTION: Amplification of the HER-2/neu (HER-2) proto-oncogene occurs in 10%-15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting growth of cancer cells. Tumor classification is determined in primary tumor tissue and metastatic biopsies. However, malignant cells tend to alter their phenotype during disease progression. Circulating tumor cell (CTC) analysis may serve as an alternative to repeated biopsies. The Food and Drug Administration-approved CellSearch system allows determination of the HER-2 protein, but not of the HER-2 gene...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27895401/her2-induced-metastasis-is-mediated-by-akt-jnk-emt-signaling-pathway-in-gastric-cancer
#20
Yiseul Choi, Young San Ko, Jinju Park, Youngsun Choi, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Douk Ho Hwang, Woo Ho Kim, Byung Lan Lee
AIM: To investigated the relationships between HER2, c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2-positive gastric cancer (GC) cells. METHODS: Immunohistochemistry was performed on tissue array slides containing 423 human GC specimens. Using HER2-positve GC cell lines SNU-216 and NCI-N87, HER2 expression was silenced by RNA interference, and the activations of JNK and AKT were suppressed by SP600125 and LY294002, respectively...
November 7, 2016: World Journal of Gastroenterology: WJG
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