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https://www.readbyqxmd.com/read/28982841/adjuvant-endocrine-therapy-for-hormone-positive-breast-cancer-focusing-on-ovarian-suppression-and-extended-treatment-an-update
#1
REVIEW
Daniel Glassman, Sue Hignett, Shazza Rehman, Richard Linforth, Mohamed Salhab
The benefits of five years of adjuvant endocrine therapy for oestrogen receptor (ER)-positive early breast cancer are well established. However, recent evidence suggests that extended endocrine treatment and ovarian suppression in selected groups of patients have significant advantages. In this article, we review the current evidence for adjuvant endocrine therapy in breast cancer with focus on extended adjuvant endocrine therapy and ovarian suppression, and also highlight the advantages and disadvantages of these therapeutic strategies...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28959637/depsidones-inhibit-aromatase-activity-and-tumor-cell-proliferation-in-a-co-culture-of-human-primary-breast-adipose-fibroblasts-and-t47d-breast-tumor-cells
#2
Suthat Chottanapund, M B M Van Duursen, Anne Zwartsen, Supatchaya Timtavorn, Panida Navasumrit, Prasat Kittakoop, Sanya Sureram, Mathuros Ruchirawat, Martin Van den Berg
Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28927154/resistance-to-the-mtor-inhibitor-everolimus-is-reversed-by-the-downregulation-of-survivin-in-breast-cancer-cells
#3
Ludovica Taglieri, Francesca De Iuliis, Anna Giuffrida, Sabrina Giantulli, Ida Silvestri, Susanna Scarpa
Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer. However, not all patients are equally sensitive to RAD001 and certain patients develop resistance. Therefore, the present study analyzed the mechanisms involved in the resistance of breast cancer cells to RAD001 in order to identify a potential tool to overcome it. The effects of RAD001 on the inhibition of cell viability, on the induction of apoptosis and autophagy and on the regulation of survivin, an anti-apoptotic protein, were evaluated in two breast cancer cell lines: BT474 (luminal B) and MCF7 (luminal A)...
September 2017: Oncology Letters
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
#4
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
https://www.readbyqxmd.com/read/28868654/impact-of-the-oatp1b1-c-521t-c-single-nucleotide-polymorphism-on-the-pharmacokinetics-of-exemestane-in-healthy-post-menopausal-female-volunteers
#5
B J Gregory, S M Chen, M A Murphy, D H Atchley, L K Kamdem
WHAT IS KNOWN AND OBJECTIVE: OATP1B1 mediates the transport of a diverse range of amphiphilic organic compounds that include bile acids, steroid conjugates and hormones. This retrospective pharmacogenetic study was conducted to assess the impact of the OATP1B1 c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthy volunteers. METHODS: Exemestane (25 mg) was administered orally to 14 healthy post-menopausal women...
October 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28865686/use-of-the-hyphenated-lc-ms-ms-technique-and-nmr-ir-spectroscopy-for-the-identification-of-exemestane-stress-degradation-products-during-the-drug-development
#6
Elżbieta U Stolarczyk, Anna Rosa, Marek Kubiszewski, Joanna Zagrodzka, Marcin Cybulski, Łukasz Kaczmarek
Exemestane (6-Methyleneandrosta-1,4-diene-3,17-dione) active pharmaceutical ingredient (EE-3) was subjected to thermal, photolytic, oxidative, acidic and base stress conditions prescribed by the ICH (International Conference on Harmonization) guideline Q1A(R2). EE-3 was found to degrade in base, acidic and oxidative conditions. Eleven new degradation products of EE-3 were characterized by the LC-MS/MS technique. One of these impurities was isolated and identified by the LC-MS/MS, NMR and IR techniques. The LC-MS/MS studies were carried out to establish fragmentation pathways of EE-3 and its new impurity...
September 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28862117/hormone-therapy-in-breast-cancer
#7
Mădălina Drăgănescu, Codruţa Carmocan
Hormonal therapy is mandatory for all patients with hormonereceptor- positive breast neoplasms. It is active both in adjuvant and metastatic disease. The only active adjuvant hormonal therapy in pre- and postmenopause is Tamoxifen. The adjuvant treatment duration influences disease-free survival, the risk of a contralateral breast cancer apparition and overall survival. The aromatase inhibitors: Anastrozol, Letrozol, Exemestan are only used in postmenopause. Fulvestrant is used in recurrent disease after or during treatment with Tamoxifen...
July 2017: Chirurgia
https://www.readbyqxmd.com/read/28817387/response-of-an-ovarian-granulosa-cell-tumor-with-everolimus-and-exemestane-after-initial-response-to-letrozole
#8
Tarek Assi, Hampig R Kourie, Elie El Rassy, Tania Moussa, Joseph Kattan
Granulosa cell tumors of the ovaries (GCTO), the most common sex cord tumors of the female genitalia, are characterized by a remarkably favorable prognosis but tend to recur even after several years of follow-up. Standard approach to manage these relapsing tumors is almost inexistent and physicians' choice is most commonly based on his/her personal expertise. Recently, the use of hormone therapy in GCTO has induced prolonged response and survival. In this case report, we report the first successful use of everolimus in the combination of exemestane to reverse the resistance to hormonal therapy with letrozole in a 53-year-old woman with GCTO...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28816986/efficacy-and-safety-of-endocrine-monotherapy-as-first-line-treatment-for-hormone-sensitive-advanced-breast-cancer-a-network-meta-analysis
#9
Jingwen Zhang, Yanhong Huang, Changyi Wang, Yuanfang He, Shukai Zheng, Kusheng Wu
BACKGROUND: Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. METHODS: We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28770670/potential-repositioning-of-exemestane-as-a-neuroprotective-agent-for-parkinson-s-disease
#10
Hyo Jin Son, Se Hee Han, Ji Ae Lee, Eun Jung Shin, Onyou Hwang
Parkinson's disease (PD) is a neurodegenerative disorder characterised by selective degeneration of the nigral dopaminergic neurons, and neuroinflammation and oxidative stress are believed to be involved in its pathogenesis. In the present study, we provide data that the synthetic steroid exemestane, which is currently being used to treat breast cancer, may be useful for PD therapy. In BV-2 microglial cells, exemestane activated the transcription factor Nrf2 and induced expression of the Nrf2-dependent genes that encode the antioxidant enzymes NAD(P)H: quinone oxidoreductase 1, haem oxygenase-1, and glutamylcysteine ligase...
June 2017: Free Radical Research
https://www.readbyqxmd.com/read/28765859/clinical-consultations-and-investigations-before-and-after-discontinuation-of-endocrine-therapy-in-women-with-primary-breast-cancer
#11
Derrick Lopez, Anna Kemp-Casey, Christobel Saunders, Elizabeth Roughead, Frances Boyle, Max Bulsara, David Preen
OBJECTIVE: Although clinical trials recommend that women with hormone-dependent primary breast cancer remain on endocrine therapy for at least 5 years, up to 60% discontinue treatment early. We determined whether these women had consulted with clinicians or had investigations for cancer recurrence or metastasis around the time they discontinued endocrine therapy, and whether clinical contact continued after discontinuation. METHODS: We performed case-control and cohort studies of women from the 45 and Up Study who were diagnosed with invasive primary breast cancer between January 2003 and December 2008, and who had ≥12 months of anastrozole, exemestane, letrozole or tamoxifen subsequently dispensed...
July 26, 2017: Public Health Research & Practice
https://www.readbyqxmd.com/read/28755088/adjuvant-endocrine-monotherapy-for-postmenopausal-early-breast-cancer-patients-with-hormone-receptor-positive-a-systemic-review-and-network-meta-analysis
#12
REVIEW
Zhu Yu, Xiaojing Guo, Yicheng Jiang, Lei Teng, Jinwu Luo, Pengfei Wang, Yunsheng Liang, Haitian Zhang
BACKGROUND: In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane, toremifene and tamoxifen. But the optimum regimen remains controversial. METHODS: PubMed, Cochrane Database and ClinicalTrials.gov were systematically reviewed of abstract for randomized-controlled trials (RCTs) to assess the efficacy of tamoxifen, letrozole, exemestane, anastrozle and toremifene for postmenopausal patients with hormone-receptor positive (HR+), who have not received prior therapy for early stage breast cancer...
July 28, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28732650/adjuvant-tamoxifen-and-exemestane-in-women-with-postmenopausal-early-breast-cancer-team-10-year-follow-up-of-a-multicentre-open-label-randomised-phase-3-trial
#13
RANDOMIZED CONTROLLED TRIAL
Marloes G M Derks, Erik J Blok, Caroline Seynaeve, Johan W R Nortier, Elma Meershoek-Klein Kranenbarg, Gerrit-Jan Liefers, Hein Putter, Judith R Kroep, Daniel Rea, Annette Hasenburg, Christos Markopoulos, Robert Paridaens, Jan B E Smeets, Luc Y Dirix, Cornelis J H van de Velde
BACKGROUND: After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial...
September 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28727815/polymorphisms-associated-with-everolimus-pharmacokinetics-toxicity-and-survival-in-metastatic-breast-cancer
#14
Tomas Pascual, María Apellániz-Ruiz, Cristina Pernaut, Cecilia Cueto-Felgueroso, Pablo Villalba, Carlos Álvarez, Luis Manso, Lucia Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona, Eva Ciruelos
PURPOSE: Metastatic breast cancer (MBC) progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS) compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs) on outcomes from this treatment through a pharmacogenetic analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28725277/sabcs-2016-systemic-therapy-for-metastatic-breast-cancer
#15
REVIEW
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Richard Greil
At the 2016 San Antonio Breast Cancer Symposium, several interesting phase II and phase III studies investigating systemic therapies for metastatic breast cancer were presented. The PrEGOC 0102 trial demonstrated that the combination of fulvestrant plus everolimus is safe and effective and could be an alternative to exemestane plus everolimus for selected patients with hormone-receptor positive, HER2-negative disease. The pan-PI3K inhibitor buparlisib showed some activity in combination with fulvestrant after failure of everolimus in the BELLE-3 trial...
2017: Memo
https://www.readbyqxmd.com/read/28715929/molecular-interactions-of-bisphenols-and-analogs-with-glucocorticoid-biosynthetic-pathway-enzymes-an-in-silico-approach
#16
Garima Verma, Mohemmed Faraz Khan, Wasim Akhtar, Mohammad Mumtaz Alam, Mymoona Akhter, Mohammad Shaquiquzzaman
Glucocorticoids are known to have vital effects on metabolism, behavior and immunity. Any sort of impairment in their synthesis may lead to the generation of numerous ill health effects. Different environmental toxicants, including bisphenols and their analogs pose deleterious effect on the biosynthesis of glucocorticoids, thereby leading to endocrine disruption. In order to assess the effect of these environmental toxicants on gluocorticoid biosynthetic pathway, an in silico study was performed. This involved molecular docking studies of 18 ligands with the selected participating enzymes of the pathway...
July 17, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28711793/efficacy-and-safety-of-everolimus-and-exemestane-in-hormone-receptor-positive-hr-human-epidermal-growth-factor-negative-her2-advanced-breast-cancer-patients-new-insights-beyond-clinical-trials-the-eva-study
#17
M E Cazzaniga, M Airoldi, V Arcangeli, S Artale, F Atzori, A Ballerio, G V Bianchi, L Blasi, S Campidoglio, M Ciccarese, M C Cursano, M Piezzo, A Fabi, L Ferrari, A Ferzi, C Ficorella, A Frassoldati, A Fumagalli, O Garrone, V Gebbia, D Generali, N La Verde, M Maur, A Michelotti, G Moretti, A Musolino, R Palumbo, M Pistelli, M Porpiglia, D Sartori, C Scavelli, A Schirone, A Turletti, M R Valerio, P Vici, A Zambelli, L Clivio, V Torri
BACKGROUND: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant...
July 13, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28711612/exemestane-loaded-alginate-nanoparticles-for-cancer-treatment-formulation-and-in-vitro-evaluation
#18
Jayapal John Joseph, Dhanaraj Sangeetha
Alginate, a biopolymer is most useful for anticancer drug delivery, because of it is biocompatible, nontoxic, biodegradable and exploiting ligand-receptor interaction. Breast cancer is spreading very fast due to the changing food habits and environmental causes. Exemestane (EXE) an oral chemotherapeutic drug was used to treat breast cancer, while loading EXE in alginate nanoparticles, the side effects which was faced during administration are expected to be reduced and control the release of exemestane. Thus, in the present study, an anticancer drug EXE was loaded into the Alginate nanoparticles (ALG-NPs) through simple controlled gelation method and evaluated in vitro to study the performance of ALG-NPs in delivering the anticancer drug EXE...
July 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28681171/a-randomized-phase-ii-trial-of-ridaforolimus-dalotuzumab-and-exemestane-compared-with-ridaforolimus-and-exemestane-in-patients-with-advanced-breast-cancer
#19
Hope S Rugo, Olivier Trédan, Jungsil Ro, Serafin M Morales, Mario Campone, Antonino Musolino, Noémia Afonso, Marta Ferreira, Kyong Hwa Park, Javier Cortes, Antoinette R Tan, Joanne L Blum, Lamar Eaton, Christine K Gause, Zhen Wang, Ellie Im, David J Mauro, Mary Beth Jones, Andrew Denker, José Baselga
PURPOSE: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. METHODS: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396)...
July 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28680952/a-review-of-fulvestrant-in-breast-cancer
#20
REVIEW
Mark R Nathan, Peter Schmid
Fulvestrant is a selective estrogen receptor degrader that binds, blocks and degrades the estrogen receptor (ER), leading to complete inhibition of estrogen signaling through the ER. This review article further explains the mechanism of action of the drug and goes on to review the trials carried out to optimize its dosing. Multiple trials have been undertaken to compare fulvestrant with other endocrine treatments, and results have shown it to have similar efficacy to anastrozole, tamoxifen and exemestane at 250 mg every 28 days...
2017: Oncology and Therapy
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