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Estrogen and breast cancer

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https://www.readbyqxmd.com/read/29352368/endocrine-therapy-and-related-issues-in-hormone-receptor-positive-early-breast-cancer-a-roundtable-discussion-by-the-breast-cancer-therapy-expert-group-bcteg
#1
REVIEW
Jame Abraham, Humberto Caldera, Robert Coleman, Anthony Elias, Matthew P Goetz, Muaiad Kittaneh, Elyse Lower, Reshma Mahtani, E Terry Mamounas, Mark Pegram, Hope Rugo, Lee Schwartzberg, Tiffany Traina, Chuck Vogel
PURPOSE: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient's comorbid conditions, actual versus perceived benefit of treatments, patient's compliance as well as financial/reimbursement issues, and long-term tolerability of therapy...
January 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29352052/estrogen-receptor-positive-breast-cancer-exploiting-signaling-pathways-implicated-in-endocrine-resistance
#2
REVIEW
Adam M Brufsky, Maura N Dickler
Advancements in molecular profiling and endocrine therapy (ET) have led to more focused clinical attention on precision medicine. These advances have expanded our understanding of breast cancer (BC) pathogenesis and hold promising implications for the future of therapy. The estrogen receptor-α is a predominant endocrine regulatory protein in the breast and in estrogen-induced BC. Successful targeting of proteins and genes within estrogen receptor (ER) nuclear and nonnuclear pathways remains a clinical goal...
January 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29351904/er%C3%AE-mediated-nuclear-sequestration-of-rsk2-is-required-for-er-breast-cancer-tumorigenesis
#3
Katarzyna A Ludwik, Oliver Gene McDonald, David R Brenin, Deborah A Lannigan
Although ribosomal protein S6 kinase A3 (RSK) activation status positively correlates with patient responses to anti-estrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of ER+ breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N-terminus to activate a pro-neoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29350274/t-lymphocytes-facilitate-brain-metastasis-of-breast-cancer-by-inducing-guanylate-binding-protein-1-expression
#4
Dana A M Mustafa, Rute M S M Pedrosa, Marcel Smid, Marcel van der Weiden, Vanja de Weerd, Alex L Nigg, Cor Berrevoets, Lona Zeneyedpour, Neibla Priego, Manuel Valiente, Theo M Luider, Reno Debets, John W M Martens, John A Foekens, Anieta M Sieuwerts, Johan M Kros
The discovery of genes and molecular pathways involved in the formation of brain metastasis would direct the development of therapeutic strategies to prevent this deadly complication of cancer. By comparing gene expression profiles of Estrogen Receptor negative (ER-) primary breast tumors between patients who developed metastasis to brain and to organs other than brain, we found that T lymphocytes promote the formation of brain metastases. To functionally test the ability of T cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB) model...
January 19, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29349764/sexual-function-post-breast-cancer
#5
Lauren Streicher, James A Simon
The consequences of estrogen deprivation and therapeutic interventions such as radiation, chemotherapy and surgery have a significant negative impact on libido, sexual arousal, orgasmic function and the ability to have pleasurable intercourse. Evaluation and treatment of female sexual dysfunction is a significant unmet need in the breast cancer survivor in spite of the availability of safe and effective treatments.
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349762/advances-in-endocrine-therapy-for-postmenopausal-metastatic-breast-cancer
#6
Lisa E Flaum, William J Gradishar
A majority of breast cancers are hormone receptor (HR) positive and are responsive to various types of hormone manipulation. Endocrine therapy is the preferred first-line therapy for patients with advanced estrogen receptor (ER) positive, HER2-negative breast cancer who do not have symptomatic visceral disease. Endocrine therapy is often continued in the second- and third-line setting, with chemotherapy deferred until tumor becomes endocrine therapy refractory and/or a visceral crisis in imminent. Therapeutic options vary based on clinical presentation and include single-agent therapies such as tamoxifen, aromatase inhibitors and fulvestrant, and combination therapies options...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349758/is-dcis-overrated
#7
Joshua Feinberg, Rachel Wetstone, Dana Greenstein, Patrick Borgen
Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC), comprises just over 20% of breast cancer cases diagnosed each year in the USA. Most patients are treated with local excision of the disease followed by whole breast radiation therapy. Total mastectomy is not an uncommon approach, and total mastectomy with a contralateral risk-reducing mastectomy has been on the rise in the past decade. In estrogen receptor-positive disease, patients are often offered endocrine ablative therapy with a selective estrogen receptor modulator or an aromatase inhibitor as both treatment and prevention...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349513/3d-qsar-study-of-steroidal-and-azaheterocyclic-human-aromatase-inhibitors-using-quantitative-profile-of-protein-ligand-interactions
#8
Sehan Lee, Mace G Barron
Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency...
January 18, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29349448/a-study-on-platinum-iv-species-containing-an-estrogen-receptor-modulator-to-reverse-tamoxifen-resistance-of-breast-cancer
#9
Weiwei Hu, Jian Zhao, Wuyang Hua, Shaohua Gou
Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and platinum(ii) drugs were designed and synthesized for targeting estrogen receptors (ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity against breast cancer cells, but also reversed the tamoxifen resistance of TamR-MCF-7 cancer cells. Computational docking assays together with cellular uptake data demonstrated that the ER ligand portion of these conjugates plays a targeting role in ER-positive tumor cells and promotes the uptake of platinum via an estrogen receptor-mediated pathway...
January 19, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29348868/luminal-like-her2-negative-stage-ia-breast-cancer-a-multicenter-retrospective-study-on-long-term-outcome-with-propensity-score-analysis
#10
Carmine De Angelis, Massimo Di Maio, Anna Crispo, Mario Giuliano, Francesco Schettini, Marta Bonotto, Lorenzo Gerratana, Donatella Iacono, Marika Cinausero, Ferdinando Riccardi, Giuseppe Ciancia, Michelino De Laurentiis, Fabio Puglisi, Sabino De Placido, Grazia Arpino
The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348811/disconnecting-the-estrogen-receptor-binding-properties-and-antimicrobial-properties-of-parabens-through-3-5-substitution
#11
Bridget L Bergquist, Kaelyn G Jefferson, Hailey N Kintz, Amorette E Barber, Andrew A Yeagley
Commercially utilized parabens are employed for their antimicrobial properties, but a weak binding to the estrogen receptor alpha (ERα) may lead to breast cancer in some applications. Modification of the paraben scaffold should allow for a disconnection of these observed properties. Toward this goal, various 3,5-substituted parabens were synthesized and assessed for antimicrobial properties against S. aureus as well as competitive binding to the ERα. The minimum inhibitory concentration assay confirmed retention of antimicrobial activity in many of these derivatives, while all compounds exhibited decreased xenoestrogen activity as determined by a combination of competitive enzyme linked immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348189/cancer-stem-cell-phenotypes-in-er-breast-cancer-models-are-promoted-by-pelp1-aib1-complexes
#12
Thu H Truong, Hsiangyu Hu, Nuri A Temiz, Kyla Hagen, Brian J Girard, Nicholas J Brady, Kathryn L Schwertfeger, Carol A Lange, Julie H Ostrander
Proline, glutamic acid, and leucine rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, interacting partners unique to cytoplasmic PELP1 and the mechanisms by which these interactions promote oncogenic PELP1 signaling were sought...
January 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29346498/association-of-treatment-for-hodgkin-lymphoma-with-estrogen-receptor-status-of-subsequent-breast-cancers
#13
Diana R Withrow, Lindsay M Morton, Rochelle E Curtis, Sara J Schonfeld, Amy Berrington de González
No abstract text is available yet for this article.
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#14
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345443/suv-calculation-in-breast-cancer-which-normalization-should-be-applied-when-using-18f-fdg-pet
#15
Olivier Humbert, Jean-Marc Riedinger, David Chardin, Isabelle Desmoulins, François Brunotte, Alexandre Cochet
BACKGROUND: When using 18F-FDG PET, glucose metabolism quantification is affected by various factors. We aimed to investigate the benefit of different SUV normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer aggressiveness and response to treatment. METHODS: Two hundred fifty-two women with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) were included. Women underwent 18F-FDG PET before and after the first course of NAC...
January 17, 2018: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29345293/s100b-expression-in-breast-cancer-as-a-predictive-marker-for-cancer-metastasis
#16
Meng-Chi Yen, Yung-Chi Huang, Jung-Yu Kan, Po-Lin Kuo, Ming-Feng Hou, Ya-Ling Hsu
In the tumor microenvironment, soluble molecules play important role in the establishment of a pre-metastatic niche. The S100 calcium-binding protein family are inflammatory molecules that contribute to the development of a pro-inflammatory tumor microenvironment. S100B belongs to the S100 family and serum S100B (also known as S100beta) serves as a marker for metastasis in lung cancer, ovarian cancer and melanoma. However, the association between S100B and the metastasis of breast cancer is not yet well understood...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345254/the-mtor-inhibitor-azd8055-overcomes-tamoxifen-resistance-in-breast-cancer-cells-by-down-regulating-hspb8
#17
Jia-Jie Shi, Si-Meng Chen, Chen-Liang Guo, Yi-Xue Li, Jian Ding, Ling-Hua Meng
Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29345201/clinical-validation-of-nuclear-factor-kappa-b-expression-in-invasive-breast-cancer
#18
Anil Kumar Agrawal, Ewa Pielka, Artur Lipinski, Michal Jelen, Wojciech Kielan, Siddarth Agrawal
Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#19
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344162/effects-of-rat-bone-marrow-derived-mesenchymal-stem-cells-on-breast-cancer-cells-with-differing-hormone-receptor-status
#20
Ying Wang, Shan Shao, Minna Luo, Shangke Huang, Lu Feng, Na Yuan, Fang Wu, Chengxue Dang, Xinhan Zhao
Breast cancer is a heterogeneous disease that can be classified into several molecular intrinsic subtypes according to hormone markers, including estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Breast cancer cases with different hormone status vary with respect to patient morbidity, metastasis organotropism and disease progression. It is well known that the most preferential relapse site of breast cancer is in the bone, but the metastatic incidence is markedly higher in hormone receptor-positive cancer compared with that in hormone receptor-negative cancers...
December 2017: Oncology Letters
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