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https://www.readbyqxmd.com/read/27923036/cotargeting-of-cyp-19-aromatase-and-emerging-pivotal-signalling-pathways-in-metastatic-breast-cancer
#1
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/27920001/a-case-report-of-pneumocystis-jiroveci-pneumonia-in-a-patient-with-metastatic-breast-cancer
#2
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/27894335/everolimus-and-exemestane-in-long-survival-hormone-receptor-positive-male-breast-cancer-case-report
#3
Z Ballatore, M Pistelli, N Battelli, A Pagliacci, M De Lisa, R Berardi, S Cascinu
BACKGROUND: Male breast cancer is a rare event, accounting for approximately 1% of all breast carcinomas. Although men with breast cancer had poorer survival when compared with women, data on prognosis principally derive from retrospective studies and from extrapolation of female breast cancer series. We reported the case of a very long survival patient. CASE PRESENTATION: A caucasian 42-year-old man underwent radical mastectomy with axillary dissection for breast cancer in 1993...
November 28, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27864574/enhancing-endocrine-therapy-combination-strategies-for-the-treatment-of-postmenopausal-hormone-receptor-positive-her2-advanced-breast-cancer
#4
REVIEW
Kathleen I Pritchard, Stephen K Chia, Christine Simmons, Deanna McLeod, Alexander Paterson, Louise Provencher, Daniel Rayson
: : Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor (HR)-positive tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR-positive, HER2-negative advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients...
November 18, 2016: Oncologist
https://www.readbyqxmd.com/read/27848887/metabolism-and-toxicological-implications-of-commonly-used-chemopreventive-drugs-against-breast-cancer-carcinogenesis
#5
Aliyu Muhammad, Mohammed Auwal Ibrahim, Ochuko Lucky Erukainure, Ibrahim Malami, Hadiza Sani, Hafsat Abdullahi Mohammed
BACKGROUND: Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy. AIM: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/carcinogenesis. METHODOLOGY: Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar...
November 16, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27843622/review-of-hormone-based-treatments-in-postmenopausal-patients-with-advanced-breast-cancer-focusing-on-aromatase-inhibitors-and-fulvestrant
#6
REVIEW
Iben Kümler, Ann S Knoop, Christina A R Jessing, Bent Ejlertsen, Dorte L Nielsen
BACKGROUND: Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer. PURPOSE: To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant. METHODS: A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included...
2016: ESMO Open
https://www.readbyqxmd.com/read/27825388/impact-of-cyp19a1-and-esr1-variants-on-early-onset-side-effects-during-combined-endocrine-therapy-in-the-text-trial
#7
Harriet Johansson, Kathryn P Gray, Olivia Pagani, Meredith M Regan, Giuseppe Viale, Valentina Aristarco, Debora Macis, Antonella Puccio, Susanne Roux, Rudolf Maibach, Marco Colleoni, Manuela Rabaglio, Karen N Price, Alan S Coates, Richard D Gelber, Aron Goldhirsch, Roswitha Kammler, Bernardo Bonanni, Barbara A Walley
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT)...
November 8, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27823654/aromatase-inhibitors-in-premenopause-great-expectations-fulfilled
#8
REVIEW
Rosalba Torrisi, Selene Rota, Agnese Losurdo, Monica Zuradelli, Giovanna Masci, Armando Santoro
Tamoxifen and GnRH analogues (GnRHa) represent the mainstay of endocrine manipulations in premenopausal women. The estrogen blockade obtained by aromatase inhibitors (AIs) plus GnRHa suppresses circulating estrogens more deeply than tamoxifen plus GnRHa. Retrospective and prospective evidence confirm a substantial activity for AIs and GnRHa in locally advanced and metastatic breast cancer. In early breast cancer inconsistent evidence emerged from 2 large randomized studies with anastrozole performing as tamoxifen in terms of DFS, but significantly worse as of OS while exemestane outperformed tamoxifen as of DFS particularly in very young and high-risk women...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27798900/what-characterizes-long-term-survivors-of-recurrent-ovarian-cancer-case-report-and-review-of-the-literature
#9
Ziad Hilal, Beate Schultheis, Franziska Hartmann, Askin Dogan, Cem Cetin, Harald Krentel, Sven Schiermeier, Clemens B Tempfer
BACKGROUND: Women with recurrent ovarian cancer have a poor prognosis and short survival. However, some women are long-term survivors and it is unclear whether they share specific common characteristics. CASE REPORT: We present the case of a 63-year-old woman with histologically-proven recurrent ovarian cancer and a survival time of 16 years after the diagnosis of recurrence. She underwent initial debulking surgery in 1994, followed by 6 cycles of adjuvant chemotherapy with cisplatin and paclitaxel...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27785059/impact-of-palbociclib-combinations-on-treatment-of-advanced-estrogen-receptor-positive-human-epidermal-growth-factor-2-negative-breast-cancer
#10
REVIEW
Katalin Boér
Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27760942/-ethinylestradiol-following-everolimus-plus-exemestane-was-effective-in-postmenopausal-endocrine-responsive-metastatic-breast-cancer-a-case-report
#11
Aya Matsuoka, Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Hiroko Yukawa, Shiho Sakaguchi, Natsuko Tanaka, Asaka Kodera, Mari Kamimura, Yoshihiko Naritaka, Tadao Shimizu
A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27758888/genetic-polymorphisms-in-the-long-noncoding-rna-mir2052hg-offer-a-pharmacogenomic-basis-for-the-response-of-breast-cancer-patients-to-aromatase-inhibitor-therapy
#12
James N Ingle, Fang Xie, Matthew J Ellis, Paul E Goss, Lois E Shepherd, Judith-Anne W Chapman, Bingshu E Chen, Michiaki Kubo, Yoichi Furukawa, Yukihide Momozawa, Vered Stearns, Kathleen I Pritchard, Poulami Barman, Erin E Carlson, Matthew P Goetz, Richard M Weinshilboum, Krishna R Kalari, Liewei Wang
Genetic risks in breast cancer remain only partly understood. Here, we report the results of a genome-wide association study of germline DNA from 4,658 women, including 252 women experiencing a breast cancer recurrence, who were entered on the MA.27 adjuvant trial comparing the aromatase inhibitors (AI) anastrozole and exemestane. Single-nucleotide polymorphisms (SNP) of top significance were identified in the gene encoding MIR2052HG, a long noncoding RNA of unknown function. Heterozygous or homozygous individuals for variant alleles exhibited a ∼40% or ∼63% decrease, respectively, in the hazard of breast cancer recurrence relative to homozygous wild-type individuals...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27739214/switching-between-endocrine-therapies-for-primary-breast-cancer-frequency-and-timing-in-australian-clinical-practice
#13
Anna Kemp-Casey, Elizabeth E Roughead, Christobel Saunders, Frances Boyle, Max Bulsara, David B Preen
AIMS: To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. METHODS: We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 (n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy...
October 14, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27733047/paradox-ca-15-3-increase-in-metastatic-breast-cancer-patients-treated-with-everolimus-a-change-of-paradigm-in-a-case-series
#14
Armando Orlandi, Carmela Di Dio, Maria Alessandra Calegari, Carlo Barone
Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15-3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15-3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth...
October 13, 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27687081/annals-express-falsely-elevated-serum-oestradiol-due-to-exemestane-therapy-a-case-report
#15
Sanja Mandic, Juergen Kratzsch, Dario Mandic, Zeljko Debeljak, Iva Lukic, Vesna Horvat, Alexander Gaudl, Vatroslav Seric
In this study we present a case of falsely elevated oestradiol (E2) concentration, determined by two immunoassays, in a breast cancer patient receiving exemestane therapy. The positive bias of immunochemical measurements was revealed using liquid chromatography tandem mass spectrometry (LC-MS/MS) which showed undetectable E2 concentration. The discrepancy is expected to be a consequence of the structural resemblance of E2 and exemestane sharing the same steroidal backbone. Inaccurate laboratory findings in therapy monitoring, as in this case, may lead to unnecessary changes of therapy...
September 28, 2016: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/27667581/plant-derived-anti-cancerous-secondary-metabolites-as-multipronged-inhibitor-of-cox-topo-and-aromatase-molecular-modeling-and-dynamics-simulation-analyses
#16
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra N Dwivedi
In the present study, 300 plant derived secondary metabolites (100 each of alkaloid, flavonoid, and terpenoid), have been screened for their anti-cancerous activity through inhibition of selected key enzymatic targets, namely cyclooxygenases (COXs), topoisomerases (Topos), and aromatase by molecular docking approach. Furthermore, the stability of the complexes of top hits, from each class of secondary metabolites, with their respective enzymatic targets was analyzed using molecular dynamics (MD) simulation analyses and binding free energy calculations...
September 25, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27549341/polymorphisms-in-drug-metabolizing-enzymes-and-steady-state-exemestane-concentration-in-postmenopausal-patients-with-breast-cancer
#17
D L Hertz, K M Kidwell, N J Seewald, C L Gersch, Z Desta, D A Flockhart, A-M Storniolo, V Stearns, T C Skaar, D F Hayes, N L Henry, J M Rae
Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 postmenopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected 2 h after exemestane dosing at a 1- or 3-month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) single-nucleotide polymorphism (SNP) would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates...
August 23, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27532364/prevalence-of-esr1-mutations-in-cell-free-dna-and-outcomes-in-metastatic-breast-cancer-a-secondary-analysis-of-the-bolero-2-clinical-trial
#18
Sarat Chandarlapaty, David Chen, Wei He, Patricia Sung, Aliaksandra Samoila, Daoqi You, Trusha Bhatt, Parul Patel, Maurizio Voi, Michael Gnant, Gabriel Hortobagyi, José Baselga, Mary Ellen Moynahan
Importance: Estrogen receptor α (ESR1) mutations found in metastatic breast cancer (MBC) promote ligand-independent receptor activation and resistance to estrogen-deprivation therapy in laboratory models. The prevalence of these mutations and their potential impact on clinical outcomes has not been established. Objective: To determine the prevalence of ESR1 mutations (Y537S and D538G) in estrogen receptor (ER)-positive MBC and determine whether mutation is associated with inferior outcomes...
October 1, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27521799/microbial-catalysed-derivatization-of-anti-cancer-drug-exemestane-and-cytotoxicity-of-resulting-metabolites-against-human-breast-adenocarcinoma-cell-line-mcf-7-in-vitro
#19
Serine Baydoun, Atia-Tul Wahab, Saira Bano, Rehan Imad, M Iqbal Choudhary
Structural transformation of anticancer drug exemestane (1) with fungi Cunninghamella blakesleeana (ATCC 8688A), Curvularia lunata (ATCC 12017), Aspergillus niger (ATCC 10549), and Gibberella fujikuroi (ATCC 10704) yielded eleven metabolites 2-12, in which 2 and 8 were identified as new. Their structures were characterized as 6-methylene-5α-androstane-3β,16β,17β-triol (2), 17β-hydroxy-6-methyleneandrosta-4-ene-3-one (3), 6α-spiroxirandrost-4-ene-3,17-dione (4), 6-methyleneandrosta-4-ene-3,17-dione (5), 6β,17β-dihydroxyandrost-4-en-3-one (6), 17β-hydroxy-6α-spiroxirandrost-1,4-diene-3-one (7), 17β-hydroxy-6α-hydroxymethylandrosta-1,4-dien-3-one (8), 6α-hydroxymethylandrosta-1,4-diene-3,17-dione (9), 17β-hydroxy-6-methyleneandrosta-1,4-diene-3,16-dione (10), 6α-hydroxy-4-androstene-3,17-dione (11), and 6α-hydroxymethylandrost-4-ene-3,17-dione (12)...
November 2016: Steroids
https://www.readbyqxmd.com/read/27479221/should-we-offer-medication-to-reduce-breast-cancer-risk-grand-rounds-discussion-from-beth-israel-deaconess-medical-center
#20
Risa B Burns, Mara A Schonberg, Nadine M Tung, Howard Libman
In November 2013, the U.S. Preventive Services Task Force issued a guideline on medications for risk reduction of primary breast cancer in women. Although mammography can detect early cases, it cannot prevent development of breast cancer. Tamoxifen and raloxifene are selective estrogen receptor modulators that have been shown to reduce the risk for estrogen receptor-positive breast cancer and are approved by the U.S. Food and Drug Administration (FDA) for this indication. However, neither medication reduces the risk for estrogen receptor-negative breast cancer or all-cause mortality...
August 2, 2016: Annals of Internal Medicine
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