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Exemestane

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https://www.readbyqxmd.com/read/28535537/triggering-of-suicidal-erythrocyte-death-by-exemestane
#1
Abdulla Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The steroidal aromatase inactivator exemestane blocks estrogen biosynthesis and is thus employed for the prevention and treatment of breast cancer. Exemestane is in part effective by stimulation of suicidal cell death or apoptosis. Side effects of exemestane treatment include anemia. At least in theory, exemestane induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
May 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534527/role-of-the-ugt2b17-deletion-in-exemestane-pharmacogenetics
#2
S Luo, G Chen, C Truica, C C Baird, K Leitzel, P Lazarus
Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of breast cancer. The major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β-D-glucuronide (17β-DHE-Gluc) by UGT2B17. The aim of the present study was to determine the effects of UGT2B17 copy number variation on the levels of urinary and plasma 17β-DHE-Gluc and 17β-DHE in patients taking EXE. Ninety-six post-menopausal Caucasian breast cancer patients with ER+ breast tumors taking 25 mg EXE daily were recruited into this study...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28512028/evaluation-of-synthesized-coumarin-derivatives-on-aromatase-inhibitory-activity
#3
Yuki Yamaguchi, Naozumi Nishizono, Daisuke Kobayashi, Teruki Yoshimura, Keiji Wada, Kazuaki Oda
In women across the world, the most common type of cancer is breast cancer. Among medical treatments, endocrine therapy based on aromatase inhibitors (AI) is expected to be effective against not only post-menopausal but also pre-menopausal breast cancer. In this study, we examined the structure-activity relationship between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives with a substituent at position 3 and coumarin derivatives with a substituent at position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values 30...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28506558/switch-to-exemestane-effective-in-early-breast-cancer
#4
Elizabeth Gourd
No abstract text is available yet for this article.
May 11, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28494403/her2-status-predicts-for-upfront-ai-benefit-a%C3%A2-trans-aiog-meta-analysis-of-12-129-patients-from%C3%A2-atac-big-1-98-and-team-with-centrally-determined-her2
#5
John M S Bartlett, Ikhlaaq Ahmed, Meredith M Regan, Ivana Sestak, Elizabeth A Mallon, Patrizia Dell'Orto, Beat Thürlimann, Caroline Seynaeve, Hein Putter, Cornelis J H Van de Velde, Cassandra L Brookes, John F Forbes, Giuseppe Viale, Jack Cuzick, Mitchell Dowsett, Daniel W Rea
BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. METHODS: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs...
May 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28473915/long-term-complete-response-in-a-breast-cancer-patient-with-skeletal-muscle-metastases-diagnosed-using-18f-fdg-pet
#6
Diana Bello-Roufai, Daniele G Soares, Khaldoun Kerrou, Ahmed Khalil, Sandrine Richard, Joseph Gligorov, Jean-Pierre Lotz
Common sites for metastatic spreading from breast cancer are bones, lungs and liver, the skeletal muscle being an unusual site. Although rare, when skeletal muscle metastases occur they are associated with a poor prognosis. These metastases are clinically difficult to diagnose since they can be found without pain symptoms. Radiologically, magnetic resonance imaging has been considered better than computed tomography for imaging of the muscles and has been the first procedure to use in case of muscle metastasis suspicion...
February 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28467729/long-term-follow-up-of-the-intergroup-exemestane-study
#7
James P Morden, Isabel Alvarez, Gianfilippo Bertelli, Alan S Coates, Robert Coleman, Lesley Fallowfield, Jacek Jassem, Stephen Jones, Lucy Kilburn, Per E Lønning, Olaf Ortmann, Claire Snowdon, Cornelis van de Velde, Jørn Andersen, Lucia Del Mastro, David Dodwell, Stig Holmberg, Hanna Nicholas, Robert Paridaens, Judith M Bliss, R Charles Coombes
Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy...
May 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28464211/osteoporosis-therapy-and-outcomes-for-postmenopausal-patients-with-hormone-receptor-positive-breast-cancer-ncic-ctg-ma-27
#8
Allan Lipton, Judith-Anne W Chapman, Kim Leitzel, Ashwani Garg, Kathleen I Pritchard, James N Ingle, G Thomas Budd, Matthew J Ellis, George W Sledge, Manuela Rabaglio, Lei Han, Catherine R Elliott, Lois E Shepherd, Paul E Goss, Suhail M Ali
BACKGROUND: Breast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self-reported osteoporosis and osteoporosis therapy (OPT) on outcomes. METHODS: The MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event-free survival (EFS), and the secondary outcome was distant disease-free survival (DDFS)...
May 2, 2017: Cancer
https://www.readbyqxmd.com/read/28463012/comparison-of-palbociclib-in-combination-with-letrozole-or-fulvestrant-with-endocrine-therapies-for-advanced-metastatic-breast-cancer-network-meta-analysis
#9
Costel Chirila, Debanjali Mitra, Ann Colosia, Caroline Ling, Dawn Odom, Shrividya Iyer, James A Kaye
BACKGROUND: Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials...
May 2, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28451964/prospective-assessment-of-patient-reported-outcomes-and-estradiol-and-drug-concentrations-in-patients-experiencing-toxicity-from-adjuvant-aromatase-inhibitors
#10
Kunal C Kadakia, Kelley M Kidwell, Nicholas J Seewald, Claire F Snyder, Anna Maria Storniolo, Julie L Otte, David A Flockhart, Daniel F Hayes, Vered Stearns, N Lynn Henry
PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole...
April 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28432226/everolimus-plus-exemestane-in-advanced-breast-cancer-safety-results-of-the-ballet-study-on-patients-previously-treated-without-and-with-chemotherapy-in-the-metastatic-setting
#11
Daniele Generali, Filippo Montemurro, Roberto Bordonaro, Antonino Mafodda, Sante Romito, Andrea Michelotti, Pierluigi Piovano, Maria Teresa Ionta, Claudia Bighin, Donata Sartori, Antonio Frassoldati, Marina Elena Cazzaniga, Ferdinando Riccardi, Franco Testore, Patrizia Vici, Carlo Antonio Barone, Alessio Schirone, Federico Piacentini, Franco Nolè, Annamaria Molino, Luciano Latini, Edda Lucia Simoncini, Fausto Roila, Francesco Cognetti, Francesco Nuzzo, Jennifer Foglietta, Alessandro Marco Minisini, Francesca Goffredo, Giuseppe Portera, Gilda Ascione, Gabriella Mariani
BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%)...
April 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28404691/exemestane-and-its-active-metabolite-17-hydroexemestane-induce-udp-glucuronosyltransferase-ugt-2b17-expression-in-breast-cancer-cells
#12
Apichaya Chanawong, Peter Ian Mackenzie, Ross A McKinnon, Dong Gui Hu, Robyn Meech
Exemestane (EXE) is an aromatase inhibitor indicated for endocrine therapy of breast cancer in post-menopausal women. The primary active metabolite of EXE, 17-hydroexemestane (17-HE), is inactivated via glucuronidation, mainly by UGT2B17. UGT2B17 also has a primary role in inactivation of endogenous androgens testosterone and dihydrotestosterone (DHT) and may play an important role in regulation of breast and prostate tumour intracrinology. We recently reported that UGT2B17 could be induced by both estrogenic and androgenic ligands in breast cancer cells via binding of the estrogen receptor alpha (ERα) or the androgen receptor (AR) to a complex regulatory unit in the proximal UGT2B17 promoter...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28400999/mtor-function-and-therapeutic-targeting-in-breast-cancer
#13
REVIEW
Stephen H Hare, Amanda J Harvey
The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. mTOR is serine/threonine kinase belonging to the phosphoinositide 3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1 and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling is often over active in multiple cancer types including breast cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28357105/osteonecrosis-of-the-jaw-associated-with-everolimus-a-case-report
#14
Daigo Yamamoto, Yu Tsubota, Toshiki Utsunomiya, Noriko Sueoka, Aiko Ueda, Kayoko Endo, Katsuhiro Yoshikawa, Masanori Kon
Everolimus, a mammalian target of rapamycin inhibitor, has recently been approved for the treatment of metastatic estrogen receptor-positive breast cancer, at a daily dose of 10 mg in combination with exemestane. Osteonecrosis of the jaw (ONJ) is a rare but severe condition, characterized by exposed necrotic bone, and is associated with various drugs that are often used to treat advanced malignancies. We herein report the case of a patient with breast cancer who developed ONJ during treatment with everolimus, which improved after discontinuation of the drug...
February 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28353061/dose-intensity-and-efficacy-of-the-combination-of-everolimus-and-exemestane-eve-exe-in-a-real-world-population-of-hormone-receptor-positive-er-pgr-her2-negative-advanced-breast-cancer-abc-patients-a-multicenter-italian-experience
#15
Mariangela Ciccarese, Alessandra Fabi, Luca Moscetti, Maria Elena Cazzaniga, Luciana Petrucelli, Rosachiara Forcignanò, Laura Isabella Lupo, Elisabetta De Matteis, Vincenzo Emanuele Chiuri, Giuseppe Cairo, Antonio Febbraro, Guido Giordano, Marianna Giampaglia, Domenico Bilancia, Nicla La Verde, Evaristo Maiello, Maria Morritti, Francesco Giotta, Vito Lorusso, Agnese Latorre, Claudio Scavelli, Sante Romito, Antonio Cusmai, Gennaro Palmiotti, Giammarco Surico
AIM: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. METHODS: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination...
March 28, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28351480/melasma-treatment-a-novel-approach-using-a-topical-agent-that-contains-an-anti-estrogen-and-a-vascular-endothelial-growth-factor-inhibitor
#16
Philip R Cohen
Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28346074/germline-genetic-predictors-of-aromatase-inhibitor-concentrations-estrogen-suppression-and-drug-efficacy-and-toxicity-in-breast-cancer-patients
#17
Daniel L Hertz, N Lynn Henry, James M Rae
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28326839/entinostat-a-promising-treatment-option-for-patients-with-advanced-breast-cancer
#18
Roisin M Connolly, Michelle A Rudek, Richard Piekarz
Entinostat is a synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, which potently and selectively inhibits class I and IV HDAC enzymes. This action promotes histone hyperacetylation and transcriptional activation of specific genes, with subsequent inhibition of cell proliferation, terminal differentiation and apoptosis. This oral HDAC inhibitor has been evaluated in Phase I and II trials in patients with advanced malignancies, and is in general well tolerated. Entinostat does not currently have regulatory approval for clinical use; however promising preclinical and clinical data exist in hormone-resistant breast cancer...
March 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28324268/a-phase-ii-study-of-combined-ridaforolimus-and-dalotuzumab-compared-with-exemestane-in-patients-with-estrogen-receptor-positive-breast-cancer
#19
José Baselga, Serafin M Morales, Ahmad Awada, Joanne L Blum, Antoinette R Tan, Marianne Ewertz, Javier Cortes, Beverly Moy, Kathryn J Ruddy, Tufia Haddad, Eva M Ciruelos, Peter Vuylsteke, Scot Ebbinghaus, Ellie Im, Lamar Eaton, Kumudu Pathiraja, Christine Gause, David Mauro, Mary Beth Jones, Hope S Rugo
PURPOSE: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). METHODS: This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857)...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28314691/prevention-of-everolimus-related-stomatitis-in-women-with-hormone-receptor-positive-her2-negative-metastatic-breast-cancer-using-dexamethasone-mouthwash-swish-a-single-arm-phase-2-trial
#20
Hope S Rugo, Lasika Seneviratne, J Thaddeus Beck, John A Glaspy, Julio A Peguero, Timothy J Pluard, Navneet Dhillon, Leon Christopher Hwang, Chaitali Nangia, Ingrid A Mayer, Timothy F Meiller, Mark S Chambers, Robert W Sweetman, J Randy Sabo, Jennifer K Litton
BACKGROUND: Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. METHODS: This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer...
March 14, 2017: Lancet Oncology
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