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https://www.readbyqxmd.com/read/28203301/progress-with-palbociclib-in-breast-cancer-latest-evidence-and-clinical-considerations
#1
REVIEW
Andrea Rocca, Alessio Schirone, Roberta Maltoni, Sara Bravaccini, Lorenzo Cecconetto, Alberto Farolfi, Giuseppe Bronte, Daniele Andreis
Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated...
February 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28197838/the-growing-role-of-cdk4-6-inhibitors-in-treating-hormone-receptor-positive-advanced-breast-cancer
#2
REVIEW
Ami N Shah, Massimo Cristofanilli
Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28183331/phase-ii-randomized-placebo-controlled-study-of-dovitinib-in-combination-with-fulvestrant-in-postmenopausal-patients-with-hr-her2-breast-cancer-that-had-progressed-during-or-after-prior-endocrine-therapy
#3
Antonino Musolino, Mario Campone, Patrick Neven, Neelima Denduluri, Carlos H Barrios, Javier Cortes, Kimberly Blackwell, Hatem Soliman, Zsuzsanna Kahan, Hervé Bonnefoi, Matthew Squires, Yong Zhang, Stephanie Deudon, Michael M Shi, Fabrice André
BACKGROUND: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor-positive (HR(+)), human epidermal growth factor receptor 2-negative (HER2(-)) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer. METHODS: In this randomized, placebo-controlled phase II trial, we evaluated whether the addition of dovitinib to fulvestrant would improve outcomes in postmenopausal patients with HR(+), HER2(-) advanced breast cancer that had progressed during or after prior ET...
February 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28166815/regulation-of-submaxillary-gland-androgen-regulated-protein-3a-via-estrogen-receptor-2-in-radioresistant-head-and-neck-squamous-cell-carcinoma-cells
#4
Jennifer Grünow, Chao Rong, Jan Hischmann, Karim Zaoui, Christa Flechtenmacher, Klaus-Josef Weber, Peter Plinkert, Jochen Hess
BACKGROUND: Molecular mechanisms of intrinsic or acquired radioresistance serve as critical barrier for curative therapy of head and neck squamous cell carcinoma (HNSCC) and remain a major obstacle for progression-free and disease-specific survival. METHODS: HNSCC cell lines were treated with a protocol of fractionated irradiation (IR, 4× 2Gy) alone or in combination with antagonists of estrogen receptor signaling and viability was determined by a colony-forming assay (CFA)...
February 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28152790/what-is-the-health-related-quality-of-life-for-women-with-metastatic-breast-cancer
#5
Amye Tevaarwerk, Hans-Peter Goertz, Mary Lou Smith, Preeti S Bajaj, Elda Railey, Carolina Reyes
: 70 Background: Metastatic breast cancer (MBC) and its treatments can have a significant impact on patients' health-related quality of life (HRQoL) and daily functioning. To better assess the impact of MBC on HRQoL, we conducted an online survey among women with MBC. METHODS: We developed and administered a cross-sectional, web-based survey, and invited registered members of three advocacy groups currently living with MBC to participate. Respondents completed an informed consent and completed assessments on symptom burden using an overall QOL question (1 item), the MD Anderson Symptom Inventory Survey (MDASI), activities of daily living (ADLs, Rotterdam Scale), and impacts on work productivity...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28147342/inhibition-of-cdk8-mediator-kinase-suppresses-estrogen-dependent-transcription-and-the-growth-of-estrogen-receptor-positive-breast-cancer
#6
Martina S J McDermott, Alexander A Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor B Roninson, Eugenia V Broude
Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer...
January 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28133341/-two-cases-of-lung-metastasis-from-breast-cancer-successfully-treated-with-endocrine-therapy
#7
Kumi Hasegawa, Yasuhiro Higashi, Ayako Kamiya, Yasushi Takatsuno, Ito Kondo, Jun Kaneko, Takeshi Endo, Shizuaki Maejima
We report 2 cases of lung metastasis from breast cancer that were successfully treated with endocrine therapy.Case 1 is a 69-year-old woman with cirrhosis of the liver caused by hepatitis C.She underwent surgery for left breast cancer at the age of 58, and surgery for right breast cancer at the age of 65.Four years later, she was diagnosed with lung metastasis of breast cancer.She received letrozole and the treatment was effective.Because the severity of the pleural effusion increased 3 years later, fulvestrant was subsequently administered...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133215/-long-term-survival-of-a-patient-with-stage-iv-breast-cancer-and-an-intrathoracic-space-occupying-metastatic-lesion
#8
Toshimori Koh, Tomohito Sakai, Shunji Kato, Shoji Hirajima, Minoru Nishio, Koji Soga, Atsushi Oguro, Noboru Nakagawa
A 50-year old woman noticed left axillary lymph node swelling and presented at our hospital. CNB showed adenocarcinoma( pap-tub, ER+, PgR+, HER2 3+). CT revealed a right lung metastatic nodule and swollen lymph nodes above the left collarbone and left axilla. However, no breast tumor was found at that time. We diagnosed occult breast cancer, TxN3bM1 (lung), Stage IV . FEC(100), paclitaxel, letrozole, anastrozole, exemestane plus trastuzumab, tegafur/uracil plus trastuzumab, and lapatinib plus capecitabine were sequentially administered...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28117994/novel-selective-estrogen-receptor-downregulators-serds-developed-against-treatment-resistant-breast-cancer
#9
Rui Xiong, Jiong Zhao, Lauren M Gutgesell, Yueting Wang, Sue Lee, Bhargava Karumudi, Huiping Zhao, Yunlong Lu, Debra A Tonetti, Gregory R J Thatcher
Resistance to the selective estrogen receptor modulator tamoxifen and to aromatase inhibitors that lower circulating estradiol occurs in up to 50% of patients, generally leading to an endocrine-independent ER+ phenotype. Selective ER downregulators (SERDs) are able to ablate ER and thus, theoretically, to prevent survival of both endocrine-dependent and -independent ER+ tumors. The clinical SERD fulvestrant is hampered by intramuscular administration and undesirable pharmacokinetics. Novel SERDs were designed using the 6-OH-benzothiophene (BT) scaffold common to arzoxifene and raloxifene...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102330/new-insights-into-fetal-mammary-gland-morphogenesis-differential-effects-of-natural-and-environmental-estrogens
#10
Lucia Speroni, Maria Voutilainen, Marja L Mikkola, Skylar A Klager, Cheryl M Schaeberle, Carlos Sonnenschein, Ana M Soto
An increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen's direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E)14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088469/estrogen-induced-expression-of-tissue-factor-pathway-inhibitor-2-in-mcf7-cells-involves-lysine-specific-demethylase-1
#11
Marianne S Andresen, Huda Omar Ali, Christiane Filion Myklebust, Per Morten Sandset, Benedicte Stavik, Nina Iversen, Grethe Skretting
Hormone-sensitive cancers can be influenced by estrogens, a process usually mediated through the estrogen receptor (ER). Tissue factor pathway inhibitor type 2 (TFPI-2) is a Kunitz-type serine protease inhibitor involved in regulating the extracellular matrix. The present study demonstrates that the expression of TFPI-2 can be induced by estrogens. Breast cancer data from GOBO displayed increased levels of TFPI-2 and increased survival in patients with ERα+ tumors. Treatment of MCF7 cells (ERα+) with 17β-estradiol (E2) or 17α-ethinyl estradiol (EE2) increased TFPI-2 mRNA and protein levels...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28074314/a-novel-effect-of-%C3%AE-adrenergic-receptor-on-mammary-branching-morphogenesis-and-its-possible-implications-in-breast-cancer
#12
Lucía Gargiulo, María May, Ezequiel M Rivero, Sabrina Copsel, Caroline Lamb, John Lydon, Carlos Davio, Claudia Lanari, Isabel A Lüthy, Ariana Bruzzone
Understanding the mechanisms that govern normal mammary gland development is crucial to the comprehension of breast cancer etiology. β-adrenergic receptors (β-AR) are targets of endogenous catecholamines such as epinephrine that have gained importance in the context of cancer biology. Differences in β2-AR expression levels may be responsible for the effects of epinephrine on tumor vs non-tumorigenic breast cell lines, the latter expressing higher levels of β2-AR. To study regulation of the breast cell phenotype by β2-AR, we over-expressed β2-AR in MCF-7 breast cancer cells and knocked-down the receptor in non-tumorigenic MCF-10A breast cells...
January 11, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28073843/active-estrogen-receptor-alpha-signaling-in-ovarian-cancer-models-and-clinical-specimens
#13
Courtney L Andersen, Matthew J Sikora, Michelle M Boisen, Tianzhou Ma, Alec Christie, George Tseng, Yong Seok Park, Soumya Luthra, Uma Chandran, Paul Haluska, Gina Mantia-Smaldone, Kunle Odunsi, Karen McLean, Adrian V Lee, Esther Elishaev, Robert P Edwards, Steffi Oesterreich
PURPOSE: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, estrogen receptor-alpha has been understudied as a target in this disease. We sought to identify hormone-responsive, estrogen receptor-alpha-dependent HGSOC. EXPERIMENTAL DESIGN: We characterized endocrine response in HGSOC cells across culture conditions (2-D, 3-D, forced suspension) and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28045951/an-experimental-analysis-of-the-molecular-effects-of-trastuzumab-herceptin-and-fulvestrant-falsodex-as-single-agents-or-in-combination-on-human-hr-her2-breast-cancer-cell-lines-and-mouse-tumor-xenografts
#14
Qing Chen, Ziyi Weng, Yunshu Lu, Yijun Jia, Longlong Ding, Fang Bai, Meixin Ge, Qing Lin, Kejin Wu
PURPOSE: To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS: Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28043824/esr1-and-its-antagonist-fulvestrant-in-pituitary-adenomas
#15
Hua Gao, Yake Xue, Lei Cao, Qian Liu, Chunhui Liu, Xiaosong Shan, Hongyun Wang, Yi Gu, Yazhuo Zhang
Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups...
December 31, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28043088/fulvestrant-for-hormone-sensitive-metastatic-breast-cancer
#16
REVIEW
Clara I Lee, Annabel Goodwin, Nicholas Wilcken
BACKGROUND: Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for women with hormone-sensitive advanced breast cancer. The goal of such systemic therapy in this setting is to reduce symptoms, improve quality of life, and increase survival time. OBJECTIVES: To assess the efficacy and safety of fulvestrant for hormone-sensitive locally advanced or metastatic breast cancer in postmenopausal women, as compared to other standard endocrine agents...
January 3, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28011460/18f-fluoroestradiol-pet-ct-measurement-of-estrogen-receptor-suppression-during-a-phase-i-trial-of-the-novel-estrogen-receptor-targeted-therapeutic-gdc-0810
#17
Yingbing Wang, Karen Ayres, Debra A Goldman, Maura N Dickler, Aditya Bardia, Ingrid A Mayer, Eric P Winer, Jill Fredrickson, Carlos L Arteaga, José Baselga, H Charles Manning, Umar Mahmood, Gary A Ulaner
PURPOSE: Evaluate 18F-fluoroestradiol (FES) PET/CT as a biomarker of estrogen receptor (ER) occupancy and/or downregulation during phase I dose escalation of the novel ER targeting therapeutic GDC-0810, and help select drug dosage for subsequent clinical trials. EXPERIMENTAL DESIGN: In a phase I clinical trial of GDC-0810, patients with ER-positive metastatic breast cancer underwent FES PET/CT before beginning therapy and at cycle 2, day 3 of GDC-0810 therapy. Up to five target lesions were selected per patient, and FES SUV corrected for background was recorded for each lesion pre-therapy and on-therapy...
December 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28011074/patient-database-analysis-of-fulvestrant-500%C3%A2-mg-in-the-treatment-of-metastatic-breast-cancer-a-european-perspective
#18
Paolo Marchetti, Nicolai Maass, Joseph Gligorov, Karin Berger, Finlay MacDougall, Jukka Montonen, Jan Lewis
INTRODUCTION: Clinical guidelines recommend that patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) should be preferentially treated with endocrine therapy. Fulvestrant (a selective estrogen receptor degrader) is approved for use in these patients following relapse after, or relapse or progression during, antiestrogen therapy. This descriptive study analyzed European treatment patterns for HR-positive MBC in real-world clinical practice. METHODS: The IMS Oncology Analyzer (OA), a retrospective cancer treatment database reporting physician-entered patient case histories, was used to identify records for postmenopausal women with HR-positive MBC from April 1, 2004 to June 30, 2013 in France, Germany, Italy, and Spain...
December 20, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28007942/everolimus-boosts-endocrine-therapy-for-breast-cancer
#19
(no author information available yet)
In a phase II trial, the mTOR inhibitor everolimus, combined with the endocrine therapy fulvestrant, improved progression-free survival in postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer who had become resistant to aromatase inhibitors.
December 22, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28000875/fulvestrant-reverses-doxorubicin-resistance-in-multidrug-resistant-breast-cell-lines-independent-of-estrogen-receptor-expression
#20
Yuan Huang, Donghai Jiang, Meihua Sui, Xiaojia Wang, Weimin Fan
Drug resistance, a major obstacle to successful cancer chemotherapy, frequently occurs in recurrent or metastatic breast cancer and results in poor clinical response. Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer. In this study, we evaluated the combination treatment of fulvestrant and doxorubicin in ER-negative multidrug-resistant (MDR) breast cancer cell lines Bads‑200 and Bats‑72. Fulvestrant potentiated doxorubicin-induced cytotoxicity, apoptosis and G2/M arrest with upregulation of cyclin B1...
February 2017: Oncology Reports
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