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Exemestane

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https://www.readbyqxmd.com/read/28654365/treatment-efficacy-adherence-and-quality-of-life-among-women-younger-than-35-years-in-the-international-breast-cancer-study-group-text-and-soft-adjuvant-endocrine-therapy-trials
#1
Poornima Saha, Meredith M Regan, Olivia Pagani, Prudence A Francis, Barbara A Walley, Karin Ribi, Jürg Bernhard, Weixiu Luo, Henry L Gómez, Harold J Burstein, Vani Parmar, Roberto Torres, Josephine Stewart, Meritxell Bellet, Antonia Perelló, Faysal Dane, Antonio Moreira, Daniel Vorobiof, Michelle Nottage, Karen N Price, Alan S Coates, Aron Goldhirsch, Richard D Gelber, Marco Colleoni, Gini F Fleming
Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS...
June 27, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28649643/molecular-stratification-of-early-breast-cancer-identifies-drug-targets-to-drive-stratified-medicine
#2
Jane Bayani, Cindy Q Yao, Mary Anne Quintayo, Fu Yan, Syed Haider, Alister D'Costa, Cassandra L Brookes, Cornelis J H van de Velde, Annette Hasenburg, Dirk G Kieback, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, Daniel Rea, Paul C Boutros, John M S Bartlett
Many women with hormone receptor-positive early breast cancer can be managed effectively with endocrine therapies alone. However, additional systemic chemotherapy treatment is necessary for others. The clinical challenges in managing high-risk women are to identify existing and novel druggable targets, and to identify those who would benefit from these therapies. Therefore, we performed mRNA abundance analysis using the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial pathology cohort to identify a signature of residual risk following endocrine therapy and pathways that are potentially druggable...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28643023/variable-aromatase-inhibitor-plasma-concentrations-do-not-correlate-with-circulating-estrogen-concentrations-in-post-menopausal-breast-cancer-patients
#3
Daniel L Hertz, Kelly A Speth, Kelley M Kidwell, Christina L Gersch, Zeruesenay Desta, Anna Maria Storniolo, Vered Stearns, Todd C Skaar, Daniel F Hayes, N Lynn Henry, James M Rae
PURPOSE: The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer. Prior work suggests that anastrozole blood concentrations are associated with the magnitude of estrogen suppression. The objective of this study was to determine whether the magnitude of estrogen suppression, as determined by plasma estradiol (E2) concentrations, in EXE or LET treated patients is associated with plasma AI concentrations...
June 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28639029/cox2-induction-a-mechanism-of-endocrine-breast-cancer-resistance
#4
Brandi L Clark, Michael A Murphy, Landry K Kamdem
PURPOSE: Urine prostaglandin E2 (PGE2) levels have shown to be a risk factor of breast cancer, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to be beneficial in preventing breast cancer risk and/or recurrence with or without aromatase inhibitors. We hypothesized that the use of an aromatase inhibitor triggers the activation of the inflammatory pathway via release of PGE2. METHODS: A single oral 25 mg dose of an aromatase inhibitor (exemestane) was given to 14 healthy postmenopausal female volunteers...
June 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28614542/use-of-anastrozole-in-the-chemoprevention-and-treatment-of-breast-cancer-a-literature-review
#5
Maria da Conceição Barros-Oliveira, Danylo Rafhael Costa-Silva, Danielle Benigno de Andrade, Umbelina Soares Borges, Cléciton Braga Tavares, Rafael Soares Borges, Janaína de Moraes Silva, Benedito Borges da Silva
Aromatase inhibitors have emerged as an alternative endocrine therapy for the treatment of hormone sensitive breast cancer in postmenopausal women. The use of third-generation inhibitors represented by exemestane, letrozol and anastrozole is currently indicated. Anastrozole is a nonsteroidal compound and a potent selective inhibitor of the aromatase enzyme. Although a few studies have shown that its pharmacodynamic and pharmacokinetic properties may be affected by interindividual variability, this drug has been recently used in all configurations of breast cancer treatment...
April 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28603633/in-vitro-metabolism-of-exemestane-by-hepatic-cytochrome-p450s-impact-of-nonsynonymous-polymorphisms-on-formation-of-the-active-metabolite-17%C3%AE-dihydroexemestane
#6
Amity Peterson, Zuping Xia, Gang Chen, Philip Lazarus
Exemestane (EXE) is an endocrine therapy commonly used by postmenopausal women with hormone-responsive breast cancer due to its potency in inhibiting aromatase-catalyzed estrogen synthesis. Preliminary in vitro studies sought to identify phase I EXE metabolites and hepatic cytochrome P450s (CYP450s) that participate in EXE biotransformation. Phase I metabolites were identified by incubating EXE with HEK293-overexpressed CYP450s. CYP450s 1A2, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5 produce 17β-dihydroexemestane (17β-DHE), an active major metabolite, as well as two inactive metabolites...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28603632/exemestane-potency-is-unchanged-by-common-nonsynonymous-polymorphisms-in-cyp19a1-results-of-a-novel-anti-aromatase-activity-assay-examining-exemestane-and-its-derivatives
#7
Amity Peterson, Zuping Xia, Gang Chen, Philip Lazarus
Exemestane (EXE) treats estrogen receptor positive (ER+) breast cancer in postmenopausal women by inhibiting the estrogen-synthesizing cytochrome P450 CYP19A1. Variability in the severity and incidence of side effects as well as overall drug efficacy may be partially explained by genetic factors, including nonsynonymous variation in CYP19A1, also known as aromatase. The present study identified phase I EXE metabolites in human liver microsomes (HLM) and investigated mechanisms that may alter the extent of systemic estrogen deprivation in EXE-treated women with breast cancer, including whether functional polymorphisms in aromatase cause differential inhibition by EXE and whether EXE metabolites possess anti-aromatase activity...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28535537/triggering-of-suicidal-erythrocyte-death-by-exemestane
#8
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...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534527/role-of-the-ugt2b17-deletion-in-exemestane-pharmacogenetics
#9
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
#10
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...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28506558/switch-to-exemestane-effective-in-early-breast-cancer
#11
Elizabeth Gourd
No abstract text is available yet for this article.
June 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
#12
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
#13
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
#14
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
#15
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
#16
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 16, 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
#17
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
#18
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%)...
June 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
#19
Apichaya Chanawong, Peter I Mackenzie, Ross A McKinnon, Dong Gui Hu, Robyn Meech
Exemestane (EXE) is an aromatase inhibitor indicated for endocrine therapy of breast cancer in postmenopausal women. The primary active metabolite of EXE, 17-hydroexemestane (17-HE), is inactivated via glucuronidation, mainly by UDP-glucuronosyltransferase 2B17 (UGT2B17). UGT2B17 also has a primary role in inactivation of endogenous androgens testosterone and dihydrotestosterone and may play an important role in regulation of breast and prostate tumor 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 α (ERα) or the androgen receptor (AR) to a complex regulatory unit in the proximal UGT2B17 promoter...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28400999/mtor-function-and-therapeutic-targeting-in-breast-cancer
#20
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
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