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https://www.readbyqxmd.com/read/27908454/fulvestrant-500-mg-versus-anastrozole-1-mg-for-hormone-receptor-positive-advanced-breast-cancer-falcon-an-international-randomised-double-blind-phase-3-trial
#1
John F R Robertson, Igor M Bondarenko, Ekaterina Trishkina, Mikhail Dvorkin, Lawrence Panasci, Alexey Manikhas, Yaroslav Shparyk, Servando Cardona-Huerta, Kwok-Leung Cheung, Manuel Jesus Philco-Salas, Manuel Ruiz-Borrego, Zhimin Shao, Shinzaburo Noguchi, Jacqui Rowbottom, Mary Stuart, Lynda M Grinsted, Mehdi Fazal, Matthew J Ellis
BACKGROUND: Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy. METHODS: In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confirmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries...
November 28, 2016: Lancet
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#2
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27895744/identification-of-targets-of-mirna-221-and-mirna-222-in-fulvestrant-resistant-breast-cancer
#3
Pengfei Liu, Manna Sun, Wenhua Jiang, Jinkun Zhao, Chunyong Liang, Huilai Zhang
The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895513/tumor-suppressor-ing4-inhibits-estrogen-receptor-activity-in-breast-cancer-cells
#4
Madeline M Keenen, Suwon Kim
Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose-response of estrogen...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27888136/different-epigenetic-mechanisms-of-er%C3%AE-implicated-in-the-fate-of-fulvestrant-resistant-breast-cancer
#5
Kouki Tsuboi, Yosuke Kaneko, Takamasa Nagatomo, Rika Fujii, Toru Hanamura, Tatsuyuki Gohno, Yuri Yamaguchi, Toshifumi Niwa, Shin-Ichi Hayashi
Approximately 70% of breast cancers express estrogen receptor α (ERα), which plays critical roles in breast cancer development. Fulvestrant has been effectively used to treat ERα-positive breast cancer, although resistance remains a critical problem. To elucidate the mechanism of resistance to fulvestrant, we established fulvestrant-resistant cell-lines named MFR (MCF-7 derived fulvestrant resistance) and TFR (T-47D derived fulvestrant resistance) from the ERα-positive luminal breast cancer cell lines MCF-7 and T-47D, respectively...
November 22, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27885811/17-%C3%AE-estradiol-inhibits-hepatitis-c-virus-mainly-by-interference-with-the-release-phase-of-its-life-cycle
#6
Andrea Magri, Matteo N Barbaglia, Chiara Z Foglia, Elisa Boccato, Michela E Burlone, Sarah Cole, Paola Giarda, Elena Grossini, Arvind H Patel, Rosalba Minisini, Mario Pirisi
BACKGROUND & AIMS: Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values...
November 7, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27879270/breast-cancer-resistance-to-antiestrogens-is-enhanced-by-increased-er-degradation-and-erbb2-expression
#7
Tomohiro Shibata, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Satoshi Hattori, Chihiro Fukumitsu, Yuichi Murakami, Ryuji Takahashi, Uhi Toh, Ken-Ichi Ito, Shigehiro Ohdo, Maki Tanaka, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono
Endocrine therapies effectively improve the outcomes of patients with estrogen receptor (ER)-positive breast cancer. However, the emergence of drug-resistant tumors creates a core clinical challenge. In breast cancer cells rendered resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27876131/chemosensitization-role-of-fulvestrant-in-combination-with-chemotherapy-in-postmenopausal-hormone-receptor-positive-and-human-epidermal-growth-factor-negative-metastatic-breast-cancer
#8
Qing-Qing Luo, Vishnu Prasad Adhikari, Chun-Xia Zhao, He Wu, Wei Dai, Xin Li, Yu-Tuan Wu, Kai-Nan Wu, Ling-Quan Kong
In metastatic breast cancer (MBC), hormone receptor positive (HR+), human epidermal growth factor negative (HER2-) subtype accounts for the majority. With various new modalities available to prolong life span in this group of patients, the effect is distant from optimum. Prevalent strategy of treating postmenopausal HR+ HER2- MBC is application of chemotherapy (CT) after progression of disease on endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients and CT works better with HR- tumor cells...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27864574/enhancing-endocrine-therapy-combination-strategies-for-the-treatment-of-postmenopausal-hormone-receptor-positive-her2-advanced-breast-cancer
#9
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/27853906/downregulation-of-estrogen-receptor-and-modulation-of-growth-of-breast-cancer-cell-lines-mediated-by-paracrine-stromal-cell-signals
#10
J Huang, P Woods, D Normolle, J P Goff, P V Benos, C J Stehle, R A Steinman
PURPOSE: Breast cancers have a poorer prognosis if estrogen receptor expression was lost during recurrence. It is unclear whether this conversion is cell autonomous or whether it can be promoted by the microenvironment during cancer dormancy. We explored the ability of marrow-derived stromal cell lines to arrest co-cultured breast cancer cells and suppress estrogen receptor alpha (ER) expression during arrest, facilitating the emergence of estrogen-independent breast cancer clones. METHODS: Cancer cell growth, ER protein, microRNA, and mRNA levels were measured in breast cancer cell lines exposed to conditioned medium from marrow stromal lines in the presence and absence of estrogen and of signaling pathway modulators...
November 16, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27845303/new-insights-into-estrogenic-regulation-of-o-6-methylguanine-dna-methyltransferase-mgmt-in-human-breast-cancer-cells-co-degradation-of-er-%C3%AE-and-mgmt-proteins-by-fulvestrant-or-o-6-benzylguanine-indicates-fresh-avenues-for-therapy
#11
Ameya Paranjpe, Nathan I Bailey, Santhi Konduri, George C Bobustuc, Francis Ali-Osman, Mohd A Yusuf, Surendra R Punganuru, Hanumantha Rao Madala, Debasish Basak, Agm Mostofa, Kalkunte S Srivenugopal
Endocrine therapy using estrogen receptor-α (ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with O(6)-methylguanine DNA methyltransferase (MGMT), a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines (MCF-7, T47D) and ER- negative cell lines (MDAMB-468, MDAMB-231), and established inhibitors of ER-α and MGMT, namely, ICI-182,780 (Faslodex) and O(6)-benzylguanine, respectively, were used to study MGMT- ER interactions...
September 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27843622/review-of-hormone-based-treatments-in-postmenopausal-patients-with-advanced-breast-cancer-focusing-on-aromatase-inhibitors-and-fulvestrant
#12
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/27798900/what-characterizes-long-term-survivors-of-recurrent-ovarian-cancer-case-report-and-review-of-the-literature
#13
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
#14
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/27765850/reactivation-of-p53-by-mdm2-inhibitor-mi-77301-for-the-treatment-of-endocrine-resistant-breast-cancer
#15
Jianfeng Lu, Donna McEachern, Shunqiang Li, Matthew J Ellis, Shaomeng Wang
Endocrine therapy has been highly effective for the treatment of estrogen-receptor positive breast cancer, but endocrine resistance develops in a significant proportion of patients. In an effort to develop novel therapeutic strategies for the treatment of endocrine resistant breast cancer, we have evaluated a potent and specific MDM2-p53 interaction inhibitor, MI-77301, which has been advanced into clinical development, for its therapeutic potential and mechanism of action in vitro and in vivo in WHIM9 and WHIM18 patient-derived xenograft (PDX) models...
October 7, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27765801/targeting-pp2a-to-overcome-enzalutamide-resistance-in-ar-breast-tumors
#16
LETTER
Ion Cristóbal, Blanca Torrejón, Manuel Pedregal, Federico Rojo, Jesús García-Foncillas
No abstract text is available yet for this article.
January 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27760945/-indoleamine-2-3-dioxygenase-activity-during-fulvestrant-therapy-for-multiple-metastatic-breast-cancer-patients
#17
Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Tomohiro Hirano, Katsuhisa Enomoto, Ryouichi Tomita, Kenji Gonda
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during fulvestrant therapyfor multiple metastatic breast cancer patients. IDO activitycan be measured using the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn were measured using high-performance liquid chromatography(HPLC). The serum Trp/Kyn level in patients with multiple metastatic breast cancer was lower than in patients without metastases. IDO activityincreased after breast cancer metastases developed. IDO activitywas correlated with the number of metastatic lesions during toremifene and fulvestrant therapy...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27760942/-ethinylestradiol-following-everolimus-plus-exemestane-was-effective-in-postmenopausal-endocrine-responsive-metastatic-breast-cancer-a-case-report
#18
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/27753529/cyclin-g2-promotes-cell-cycle-arrest-in-breast-cancer-cells-responding-to-fulvestrant-and-metformin-and-correlates-with-patient-survival
#19
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27748765/genomic-modelling-of-the-esr1-y537s-mutation-for-evaluating-function-and-new-therapeutic-approaches-for-metastatic-breast-cancer
#20
A Harrod, J Fulton, V T M Nguyen, M Periyasamy, L Ramos-Garcia, C-F Lai, G Metodieva, A de Giorgio, R L Williams, D B Santos, P J Gomez, M-L Lin, M V Metodiev, J Stebbing, L Castellano, L Magnani, R C Coombes, L Buluwela, S Ali
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations...
October 17, 2016: Oncogene
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