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Aromatase inhibitor

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https://www.readbyqxmd.com/read/29679775/influence-of-side-effects-on-early-therapy-persistence-with-letrozole-in-post-menopausal-patients-with-early-breast-cancer-results-of-the-prospective-evaluate-tm-study
#1
N Nabieva, T Fehm, L Häberle, J de Waal, M Rezai, B Baier, G Baake, H-C Kolberg, M Guggenberger, M Warm, N Harbeck, R Wuerstlein, J-U Deuker, P Dall, B Richter, G Wachsmann, C Brucker, J W Siebers, M Popovic, T Kuhn, C Wolf, H-W Vollert, G-P Breitbach, W Janni, R Landthaler, A Kohls, D Rezek, T Noesselt, G Fischer, S Henschen, T Praetz, V Heyl, T Kühn, T Krauss, C Thomssen, A Hohn, H Tesch, C Mundhenke, A Hein, C C Hack, K Schmidt, E Belleville, S Y Brucker, S Kümmel, M W Beckmann, D Wallwiener, P Hadji, P A Fasching
BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study...
April 18, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29670855/current-therapies-for-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-patients
#2
REVIEW
Alexey A Larionov
The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29667754/estrogen-regulated-expression-of-p450arom-genes-in-the-brain-and-ovaries-of-adult-female-indian-climbing-perch-anabas-testudineus
#3
Puja Pal, Sujata Roy Moulik, Shreyasi Gupta, Payel Guha, Suravi Majumder, Sourav Kundu, Buddhadev Mallick, Kousik Pramanick, Dilip Mukherjee
Cytochrome P450arom (CYP19), a product of cyp19a1 gene, catalyzes the conversion of androgens to estrogens and is essential for regulation of reproductive function in vertebrates. In the present study, we isolated partial cDNA encoding the ovarian (cyp19a1a) and brain (cyp19a1b) P450arom genes from adult female perch, Anabas testudineus and investigated their regulation by estrogen in vivo. Results demonstrated that cyp19a1a and cyp19a1b predominate in ovary and brain respectively, with quantity of both attuned to reproductive cycle...
April 18, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/29666928/implications-of-esr1-mutations-in-hormone-receptor-positive-breast-cancer
#4
REVIEW
Tomás Reinert, Rodrigo Gonçalves, José Bines
Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment...
April 17, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29665500/aromatase-inhibition-by-letrozole-attenuates-kainic-acid-induced-seizures-but-not-neurotoxicity-in-mice
#5
Ramsha Iqbal, Gaurav K Jain, Fouzia Siraj, Divya Vohora
Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid...
April 9, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29664714/randomized-phase-ii-trial-of-fulvestrant-plus-everolimus-or-placebo-in-postmenopausal-women-with-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-metastatic-breast-cancer-resistant-to-aromatase-inhibitor-therapy-results-of-pre0102
#6
Noah Kornblum, Fengmin Zhao, Judith Manola, Paula Klein, Bhuvaneswari Ramaswamy, Adam Brufsky, Phillip J Stella, Brian Burnette, Melinda Telli, Della F Makower, Puneet Cheema, Cristina I Truica, Antonio C Wolff, Gamini S Soori, Barbara Haley, Timothy R Wassenaar, Lori J Goldstein, Kathy D Miller, Joseph A Sparano
Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo...
April 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29662534/obesity-and-outcome-of-post-menopausal-women-receiving-adjuvant-letrozole-for-breast-cancer
#7
Jamal Zekri, Kamel Farag, Ahmed Allithy
Introduction: Aromatase enzyme activity is predominant in adipose tissue. This has led to speculation that aromatase activity is elevated in obese women and subsequently decreased the clinical activity of adjuvant aromatase inhibitors (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We investigated the effect of obesity on the outcome of this population. Patients and methods: Records of 320 consecutive post-menopausal (PM) women with ER+ BC starting single agent adjuvant letrozole between years 2005 and 2014 were retrospectively reviewed...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29657704/successful-treatment-of-three-synchronous-primary-malignant-tumours-reflection-on-surgical-pathological-and-oncological-aspects-and-decision-making
#8
Emese Irma Ágoston, Áron Somorácz, Lilla Madaras, Attila Zaránd, Gyöngyvér Szentmártoni, Zsuzsanna Orosz, Magdolna Dank, Zsolt Baranyai
We report a case of a patient with triple synchronous primary malignancies (breast, colon, kidney) which has not been previously reported in the literature. A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left breast with axillary lymph node metastasis. During the staging period, renal cell carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon were found. Since the breast tumour demonstrated favourable biology, aromatase inhibitor therapy had been started and simultaneous right colectomy and left nephrectomy was performed...
April 2018: Journal of Surgical Case Reports
https://www.readbyqxmd.com/read/29651409/incidence-of-comorbidities-in-women-with-breast-cancer-treated-with-tamoxifen-or-an-aromatase-inhibitor-an-australian-population-based-cohort-study
#9
Huah Shin Ng, Bogda Koczwara, David Roder, Theo Niyonsenga, Agnes Vitry
Background: The development of comorbidities has become increasingly relevant with longer-term cancer survival. Objective: To assess the pattern of comorbidities among Australian women with breast cancer treated with tamoxifen or an aromatase inhibitor. Design: Retrospective cohort study using Pharmaceutical Benefits Scheme (PBS) data (10% sample) from January 2003 to December 2014. Dispensing claims data were used to identify comorbidities and classified with the Rx-Risk-V model...
2018: Journal of Comorbidity
https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#10
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29644889/comparing-exercise-responses-to-aerobic-plus-resistance-training-between-postmenopausal-breast-cancer-survivors-undergoing-aromatase-inhibitor-therapy-and-healthy-women
#11
Thais R S de Paulo, Kerri M Winters-Stone, Juliana Viezel, Fabricio E Rossi, Bruna L Aro, Ana Carolina A C Trindade, Jamile S Codogno, Ismael F Freitas Junior
BACKGROUND: The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. METHODS: The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO2 max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively...
April 12, 2018: Disability and Rehabilitation
https://www.readbyqxmd.com/read/29644007/impact-of-adjuvant-hormonotherapy-on-radiation-induced-breast-fibrosis-according-to-the-individual-radiosensitivity-results-of-a-multicenter-prospective-french-trial
#12
Céline Bourgier, Florence Castan, Olivier Riou, Tan-Dat Nguyen, Karine Peignaux, Claire Lemanski, Jean-Léon Lagrange, Youlia Kirova, Eric Lartigau, Yazid Belkacemi, Sofia Rivera, Georges Noël, Sébastien Clippe, Françoise Mornex, Christophe Hennequin, Sophie Gourgou, Muriel Brengues, Pascal Fenoglietto, Esat Mahmut Ozsahin, David Azria
Background: To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). Results: HT- and RILAhigh were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILAlow and HT+ than in patients with RILAhigh and HT- (75.8% and 100%, respectively; p = 0...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29642911/gnrh-dysregulation-in-polycystic-ovarian-syndrome-pcos-is-a-manifestation-of-an-altered-neurotransmitter-profile
#13
Nirja Chaudhari, Mitali Dawalbhakta, Laxmipriya Nampoothiri
BACKGROUND: GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS...
April 11, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29627127/the-action-of-estrogens-and-progestogens-in-the-young-female-breast
#14
Irene Zolfaroli, Juan J Tarín, Antonio Cano
Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors...
March 28, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29626484/neuroestradiol-in-regulation-of-gnrh-release
#15
REVIEW
Ei Terasawa
The concept that the positive feedback effect of ovarian estradiol (E2 ) results in GnRH and gonadotropin surges is a well-established principle. However, a series of studies investigating the rapid action of E2 in female rhesus monkeys has led to a new concept that neuroestradiol, synthesized and released in the hypothalamus, also contributes to regulation of the preovulatory GnRH surge. This unexpected finding started from our surprising observation that E2 induces rapid stimulatory action in GnRH neurons in vitro...
April 4, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29623577/use-of-dual-mtor-inhibitor-mln0128-against-everolimus-resistant-breast-cancer
#16
Karineh Petrossian, Duc Nguyen, Chiao Lo, Noriko Kanaya, George Somlo, Yvonne Xiaoyong Cui, Chiun-Sheng Huang, Shiuan Chen
PURPOSE: HR+/HER2- aromatase inhibitor-resistant metastatic breast cancer can be treated with everolimus and a second AI until the cancer recurs. Targeting these everolimus-resistant patients with the latest standard of care, CDK4/6 inhibitors, has not been clearly addressed. Understanding the signaling transduction pathways, which everolimus resistance activates, will elucidate the mechanisms and offer treatment strategies of everolimus resistance. METHODS: To mimic the clinical setting, letrozole-resistant cells were used to generate an everolimus-resistant model (RAD-R)...
April 5, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29621580/use-of-nutritional-supplements-contaminated-with-banned-doping-substances-by-recreational-adolescent-athletes-in-athens-greece
#17
Konstantinos Tsarouhas, Nassia Kioukia-Fougia, Petros Papalexis, Aristidis Tsatsakis, Dimitrios Kouretas, Flora Bacopoulou, Christina Tsitsimpikou
Although the use of nutritional supplements by adult athletes has been extensively studied, information on supplements consumption by adolescent athletes is still limited. The present study reports on the use of nutritional supplements contaminated with banned doping substances among 170 recreational adolescent athletes from eleven, randomly selected, gym centres, in Athens, Greece. Nutritional supplements consumption was reported by almost 60% of the study population, with proteins/amino acids and vitamins being the most popular...
April 2, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29620427/blocking-oestradiol-synthesis-pathways-with-potent-and-selective-coumarin-derivatives
#18
Sanna Niinivehmas, Pekka A Postila, Sanna Rauhamäki, Elangovan Manivannan, Sami Kortet, Mira Ahinko, Pasi Huuskonen, Niina Nyberg, Pasi Koskimies, Sakari Lätti, Elina Multamäki, Risto O Juvonen, Hannu Raunio, Markku Pasanen, Juhani Huuskonen, Olli T Pentikäinen
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5 µM and, furthermore, three of them produced ≥68% inhibition at 1 µM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29619093/aromatase-inhibitors-are-associated-with-a-higher-fracture-risk-than-tamoxifen-a-systematic-review-and-meta-analysis
#19
REVIEW
Olivia L Tseng, John J Spinelli, Carolyn C Gotay, Wan Y Ho, Mary L McBride, Martin G Dawes
Background: In this paper, our aim was to systematically evaluate published evidence of bone fracture risk associated with tamoxifen and aromatase inhibitors in women aged 65 and under, and diagnosed with nonmetastatic breast cancer. Methods: We comprehensively searched MEDLINE, EMBASE and CINAHL databases from January 1997 through May 2015, and reference lists of the selected articles to identify English-language randomized controlled trials and cohort studies of fracture risk...
April 2018: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/29610032/personalized-prevention-in-high-risk-individuals-managing-hormones-and-beyond
#20
D Gareth Evans, Sacha J Howell, Anthony Howell
Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold...
March 30, 2018: Breast: Official Journal of the European Society of Mastology
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