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https://www.readbyqxmd.com/read/29792845/current-frontline-endocrine-treatment-options-for-women-with-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-her2-negative-advanced-stage-breast-cancer
#1
REVIEW
Hikmat N Abdel-Razeq
Despite the recent advances in breast cancer early detection and awareness, a significant portion of patients present with an advanced-stage disease and more patients will progress to stage IV despite adequate treatment of their initial early-stage disease. Hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor-2 (HER2)-negative subtype is the commonest among all breast cancer subtypes. The management of the advanced-stage disease of this subtype has evolved significantly over the past few years...
May 19, 2018: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29787591/pharmacophore-modeling-for-identification-of-anti-igf-1r-drugs-and-in-vitro-validation-of-fulvestrant-as-a-potential-inhibitor
#2
Samra Khalid, Rumeza Hanif, Ishrat Jabeen, Qaisar Mansoor, Muhammad Ismail
Insulin-like growth factor 1 receptor (IGF-1R) is an important therapeutic target for breast cancer treatment. The alteration in the IGF-1R associated signaling network due to various genetic and environmental factors leads the system towards metastasis. The pharmacophore modeling and logical approaches have been applied to analyze the behaviour of complex regulatory network involved in breast cancer. A total of 23 inhibitors were selected to generate ligand based pharmacophore using the tool, Molecular Operating Environment (MOE)...
2018: PloS One
https://www.readbyqxmd.com/read/29783894/fulvestrant-in-management-of-hormone-receptor-positive-metastatic-breast-cancer
#3
Maryam Nemati Shafaee, Matthew James Ellis
Fulvestrant is a steroidal selective estrogen receptor degrader that was approved by the US FDA in 2002 for treatment of ER-positive metastatic breast cancer (ER + MBC) post-progression on aromatase inhibitors. In 2016, the label was updated to include endocrine therapy naive ER + MBC. While initially fulvestrant was thought to be equivalent to aromatase inhibitors with monthly dose of 250 mg intramuscular injection, several postmarketing trials challenged this understanding. Subsequently, the recommended dose changed to 500 mg monthly plus loading dose, and this was proven to be superior to anastrozole in efficacy...
May 22, 2018: Future Oncology
https://www.readbyqxmd.com/read/29783719/in-vitro-estrogenic-and-breast-cancer-inhibitory-activities-of-chemical-constituents-isolated-from-rheum-undulatum-l
#4
Dahae Lee, SeonJu Park, Sungyoul Choi, Seung Hyun Kim, Ki Sung Kang
We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29783185/impact-of-body-mass-index-on-the-efficacy-of-endocrine-therapy-in-patients-with-metastatic-breast-cancer-a-retrospective-two-center-cohort-study
#5
Luwam Zewenghiel, Henrik Lindman, Antonis Valachis
BAKGROUND: The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant. METHODS: A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified...
May 18, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29781326/progression-free-survival-with-endocrine-based-therapies-following-progression-on-non-steroidal-aromatase-inhibitor-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-a-network-meta-analysis
#6
Rajeev Ayyagari, Derek Tang, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, David Chandiwana, Anand A Dalal, Polly Ann Niravath
OBJECTIVE: To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with HR+/HER2- mBC after NSAI progression. DESIGN: network meta-analysis (NMA) Methods: Randomized clinical trials of ETs for HR+/HER2- mBC were identified via a systematic literature review using Medline, EMBASE, Cochrane Library, and key conference proceedings. All trials met the following inclusion criteria: 1) included women with HR+/HER2- mBC, 2) previous treatment with ETs or chemotherapy as first-line therapy, 3) treatment with ET as monotherapy or in combination with targeted therapy, 4) PFS was reported, and 5) published in 2007 (when HER2 testing became standardized) or later...
May 21, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29780257/effect-of-first-line-endocrine-therapy-in-patients-with-hormone-sensitive-advanced-breast-cancer-a-network-meta-analysis
#7
Tingting Zhang, Fubin Feng, Wenge Zhao, Jinhui Tian, Yan Yao, Chao Zhou, Shengjie Dong, Congcong Wang, Chuanxin Zang, Qingliang Lv, Changgang Sun
Background: Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. Materials and methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29778787/efficacy-of-palbociclib-combinations-in-hormone-receptor-positive-metastatic-breast-cancer-patients-after-prior-everolimus-treatment
#8
Ajay Dhakal, Christina M Matthews, Ellis Glenn Levine, Kilian Elizabeth Salerno, Fan Zhang, Kazuaki Takabe, Amy P Early, Stephen B Edge, Tracy O'Connor, Thaer Khoury, Jessica S Young, Mateusz Opyrchal
PURPOSE: Outcome data on hormone receptor positive (HR+ ), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2- ) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+ HER2- MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+ HER2- MBC with prior exposure to everolimus while receiving palbociclib-based therapy...
April 28, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#9
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29768351/the-cdk4-6-inhibitor-in-hr-positive-advanced-breast-cancer-a-systematic-review-and-meta-analysis
#10
Wu Ding, Zhian Li, Caiyun Wang, GuoDong Ruan, LuPing Chen, Chuanjian Tu
BACKGROUND: Recently, several high-quality clinical randomized controlled trials (RCTs) have identified that cyclin-dependent kinases (CDKs) 4/6 inhibitors obtained a great safety and efficacy, which can be consequently applied as a combination therapy with letrozole or fulvestrant for women who had advanced breast cancer and progressed while receiving endocrine therapy. In this systemic review, we performed a meta-analysis to explore whether CDK4/6 inhibitors had a significantly benefit to treating hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2 negative (HER2-negative) advanced breast cancer...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29749272/fulvestrant-for-the-treatment-of-advanced-breast-cancer
#11
Sophie A Blackburn, Ruth M Parks, Kwokleung Cheung
The current issues with endocrine therapy for treatment of advanced breast cancer include balance of efficacy of therapy versus tolerability as well as hormone resistance. The efficacy of fulvestrant, a selective oestrogen receptor degrader (SERD), has been demonstrated in hormone receptor positive patients previously untreated or treated with hormonal therapy. Areas covered: This article discusses the journey of fulvestrant licensing, its efficacy in combination with other endocrine therapies and the future role it may have within breast cancer treatment...
May 11, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29745344/selection-of-g1-paba-as-a-gper1-ligand-compared-to-phenol-red-via-a-ligand-based-virtual-screening-coupled-to-molecular-dynamics-simulations-and-its-anti-proliferative-effects-on-breast-cancer-cells
#12
Correa-Basurto Jose, Jose G Trujillo-Ferrara, Mendoza-Lujambio Irene, Duenas-Gonzalez Alfonso, Chavez-Blanco Alma, Martinez-Archundia Marlet, M Bello, Garcia Sanchez Jose Ruben, Fragoso-Vazquez Manuel Jonathan, Mendez-Luna David, Prestegui-Martel Berenice, Martinez-Munoz Alberto
Recent reports have demonstrated the role of the G protein-coupled estrogen receptor (GPER1) on the growth and proliferation of breast cancer cells. The coupling of GPER1 to estrogen, tamoxifen or fulvestrant triggers cellular signaling pathways (PI3K and ERK) related to cell proliferation. In an effort to develop new therapeutic strategies against breast cancer, we performed an in silico study to explore the binding pose of a set of designed G15 and G1 analogue compounds, including phenol red. First, we included a carboxyl group instead of the acetyl group from G1 to form amides with several moieties to increase the affinity for GPER1...
May 10, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29726787/role-of-cyclin-dependent-kinase-4-6-inhibitors-in-the-current-and-future-eras-of-cancer-treatment
#13
S Parylo, A Vennepureddy, V Dhar, P Patibandla, A Sokoloff
Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29707743/cost-effectiveness-of-second-line-endocrine-therapies-in-postmenopausal-women-with-hormone-receptor-positive-and-human-epidermal-growth-factor-receptor-2-negative-metastatic-breast-cancer-in-japan
#14
Verin Lertjanyakun, Nathorn Chaiyakunapruk, Susumu Kunisawa, Yuichi Imanaka
BACKGROUND: Exemestane (EXE), exemestane + everolimus (EXE + EVE), toremifene (TOR), and fulvestrant (FUL) are second-line endocrine therapies for postmenopausal hormone receptor-positive (HR +)/human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (mBC) in Japan. Although the efficacy of these therapies has been shown in recent studies, cost-effectiveness has not yet been determined in Japan. OBJECTIVE: This study aimed to examine the cost-effectiveness of second-line endocrine therapies for the treatment of postmenopausal women with HR + and HER2 - mBC...
April 30, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29703823/everolimus-enhances-the-efficacy-of-fulvestrant-in-er-breast-cancer
#15
(no author information available yet)
mTOR inhibition with everolimus extends progression-free survival in combination with fulvestrant.
April 27, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29683499/the-role-of-androgens-on-periodontal-repair-in-female-rats
#16
João Paulo Steffens, Luis Carlos Leal Santana, Jonleno Coutinho Paiva Pitombo, Daniel Olivio Ribeiro, Maria Carolina Costa Albaricci, Stephanie von Stein Cubas Warnavin, Alpdogan Kantarci, Luis Carlos Spolidorio
BACKGROUND: Testosterone replacement enhances cognitive function and musculoskeletal health in postmenopausal women. However, the biological role of testosterone on inflammation and bone metabolism in females is not well understood. Our objective was to measure the impact of androgens and their receptors on periodontal tissues during periodontal repair in female rats. METHODS: Seventy female Holtzman rats were divided into seven groups (n = 10/group): negative control; repair control; androgen receptor antagonist (flutamide, 50 mg/kg, every other day); estrogen receptor antagonist (fulvestrant, 1...
April 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29676477/influence-of-estrogen-deficiency-on-guided-bone-augmentation-investigation-of-rat-calvarial-model-and-osteoblast-like-mc3t3-e1-cells
#17
Tatsuya Kubota, Akira Hasuike, Naoya Tsukune, Yasumasa Ozawa, Takanobu Yamamoto, Seiko Min, Masako Naito, Shuichi Sato
The effect of estrogen deficiency in bone augmentation, and the mechanisms by which estrogen deficiency impedes osteoblast differentiation and collagen matrix production, were examined. Twenty female Jcl:Wistar rats were divided into two groups: ovariectomized rats; and control rats. Guided bone augmentation was performed by positioning plastic caps in the calvarium of all animals at 8 wk after ovariectomy or sham surgery. Micro-computed tomography and histological sections were used to determine the amount of bone augmentation within the plastic caps...
April 20, 2018: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29672735/parallel-factor-chip-provides-essential-internal-control-for-quantitative-differential-chip-seq
#18
Michael J Guertin, Amy E Cullen, Florian Markowetz, Andrew N Holding
A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery...
April 17, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29670855/current-therapies-for-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-patients
#19
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/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
#20
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
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