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Am J Physiol Cell Physiol 2018 Dec 12. Epub 2018 Dec 12.

Faculty of Health and Sport Sciences, The University of Tokyo, Waseda University, Japan.

The contractile and metabolic properties of adult skeletal muscle change in response to endurance exercise. The mechanisms of transcriptional regulation in exercise-induced skeletal muscle adaptation, including fiber-type switching and mitochondrial biogenesis, have been investigated intensively, whereas the role of microRNA (miRNA)-mediated posttranscriptional gene regulation is less well understood. We used tamoxifen-inducible Dicer1 knockout (iDicer KO) mice to reduce the global expression of miRNAs in adult skeletal muscle and subjected these mice to 2 weeks of voluntary wheel running. Read More

Wien Med Wochenschr 2018 Dec 11. Epub 2018 Dec 11.

General Practice Department, Faculty of Medicine, Strasbourg University, Strasbourg, France.

Background: Nearly half of patients discontinue tamoxifen hormone therapy early because of side effects, thus increasing the risk of breast cancer recurrence. Could a homeopathic treatment improve compliance?

Methods: A patient suffering from side effects of tamoxifen was seen in consultation every 2 months for 10 months by a senior homeopathic doctor and a registrar.

Results: Case analysis and repertorisation led to the identification of Pulsatilla as the simillimum drug and tamoxifen 7c as the etiological treatment. Read More

EMBO Rep 2018 Dec 11. Epub 2018 Dec 11.

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.

EMBO Rep 2018 Dec 11. Epub 2018 Dec 11.

Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK

The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism. Read More

EMBO Rep 2018 Dec 11. Epub 2018 Dec 11.

Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen-positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross-linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein-coupled estrogen receptor (GPER) and hypoxia-inducible factor-1 alpha (HIF-1A). Read More

J Cell Physiol 2018 Dec 7. Epub 2018 Dec 7.

Department of General Surgery, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Tamoxifen treatment is important assistant for estrogen-receptor-positive breast cancer (BRCA) after resection. This study aimed to identify signatures for predicting the prognosis of patients with BRCA after tamoxifen treatment. Data of gene-specific DNA methylation (DM), as well as the corresponding clinical data for the patients with BRCA, were obtained from The Cancer Genome Atlas and followed by systematic bioinformatics analyses. Read More

Biomed Chromatogr 2018 Dec 9:e4462. Epub 2018 Dec 9.

Unidad de Investigación Médica Yucatan, Unidad Médica de Alta Especialidad, Centro Médico Ignacio García Téllez, Instituto Mexicano del Seguro Social, Merida, Yucatan, Mexico.

To date, several methods for quantification of tamoxifen and its metabolites have been developed, most of which employ liquid chromatography tandem-mass spectrometry (LC-MS/MS). These methods are highly sensitive and reproducible, but are also time-consuming and require expensive equipment; one of its main disadvantages is matrix ionization effects. A more viable option, particularly in developing countries, is high-performance liquid chromatography (HPLC) coupled with UV or fluorescence detection (FLD). Read More

Rev Bras Ginecol Obstet 2018 Dec 7;40(12):794-799. Epub 2018 Dec 7.

School of Medicine, Department of Health Sciences, Faculdade Mauricio de Nassau, Cabo de Santo Agostinho, Recife, PE, Brazil.

Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMX is the development of drug resistance caused by molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 () polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of polymorphisms and how they can affect the results of TMX in breast cancer treatment. Read More

Front Cell Neurosci 2018 23;12:452. Epub 2018 Nov 23.

Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing, China.

The cortex consists of 100s of neuronal subtypes that are organized into distinct functional regions; however, the mechanisms underlying cell fate determination remain unclear. is involved in several developmental processes, including telencephalic patterning, cell proliferation and cell fate determination. Constitutive disruption of leads to the transformation of cortical neurons into Cajal-Retzius (CR) cells, accompanied by a substantial expansion of the cortical hem through the consumption of the cortex. Read More

Nat Genet 2018 Dec 10. Epub 2018 Dec 10.

Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.

Seventy percent of breast cancers express the estrogen receptor (ER), and agents that target the ER are the mainstay of treatment. However, virtually all people with ER breast cancer develop resistance to ER-directed agents in the metastatic setting. Beyond mutations in the ER itself, which occur in 25-30% of people treated with aromatase inhibitors, knowledge about clinical resistance mechanisms remains incomplete. Read More

Pancreas 2019 Jan;48(1):22-35

Digestive Disease Institute, Gastroenterology and Hepatology Department, Cleveland Clinic, Cleveland, OH.

Objectives: The aim of our study was to investigate the cases of drug-induced acute pancreatitis (DIAP) with hypertriglyceridemia as the mechanism of injury.

Methods: A MEDLINE search (1963-2018) of the English language literature was performed looking for all human case reports of adults (>18 years old) with hypertriglyceridemia as the mechanism of DIAP. The latest search date was February 28, 2018. Read More

Comput Biol Chem 2018 Nov 30;78:153-164. Epub 2018 Nov 30.

Department of Chemistry, St. Berchmans College (Autonomous), Changanasserry, Kerala, India.

A derivative of naphthaquinone, 2-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione (DPDHN) was synthesized from lawsone by ultrasound accelerated technique. The compound was characterized by elemental analysis, IR, UV-vis, NMR and mass spectral studies. Single crystal X-ray diffraction studies revealed that the compound crystallized in monoclinic space group P2/c. Read More

Breast Cancer Res 2018 Dec 10;20(1):149. Epub 2018 Dec 10.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Tamoxifen treatment greatly reduces a woman's risk of developing a second primary breast cancer. There is, however, substantial variability in treatment response, some of which may be attributed to germline genetic variation. CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. Read More

Neurobiol Learn Mem 2018 Dec 3;157:79-85. Epub 2018 Dec 3.

Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, United States. Electronic address:

HIF-1α is a hypoxia-inducible protein that regulates many cellular processes, including neural stem cell maintenance. Previous work demonstrated constitutive stabilization of HIF-1α in neural stem cells (NSCs) of the adult mouse subventricular zone (SVZ) and hippocampal subgranular zone (SGZ). Genetic inactivation of NSC-encoded HIF-1α in the adult SVZ results in gradual loss of NSCs, but whether HIF-1α is required for the maintenance of SGZ hippocampal progenitors and adult hippocampal neurogenesis has not been determined. Read More

Cochrane Database Syst Rev 2018 Dec 4;12:CD009458. Epub 2018 Dec 4.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section Three, Ren Min Nan Lu Avenue, Chengdu, Sichuan, China, 610041.

Background: Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. Read More

Onco Targets Ther 2018 9;11:8001-8012. Epub 2018 Nov 9.

Department of Internal Medicine,

Background: Breast cancer is still one of the major public health burdens worldwide, although there is tremendous progress in early diagnosis and treatment of breast cancer. Tamoxifen was one of the most popular endocrine therapies for early-stage estrogen receptor (ER) + breast cancer patients. However, a high incidence of drug resistance develops along with poor prognosis in breast cancer. Read More

Oncologist 2018 Dec 5. Epub 2018 Dec 5.

Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: The diagnosis of mixed invasive ductal and lobular carcinoma (IDC-L) in clinical practice is often associated with uncertainty related to its prognosis and response to systemic therapies. With the increasing recognition of invasive lobular carcinoma (ILC) as a distinct disease subtype, questions surrounding IDC-L become even more relevant. In this study, we took advantage of a detailed clinical database to compare IDC-L and ILC regarding clinicopathologic and treatment characteristics, prognostic power of histologic grade, and survival outcomes. Read More

Cancer Discov 2018 Dec 5. Epub 2018 Dec 5.

Stem Cells and Cancer Division, The Walter and Eliza Hall Institute.

Venetoclax, a potent and selective BCL-2 inhibitor, synergizes with endocrine therapy in pre-clinical models of ER-positive breast cancer. Using a phase 1b 3+3 dose escalation and expansion study design, 33 patients with ER and BCL-2-positive metastatic disease (mean prior regimens, 2; range 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated 'on-target' lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase 2 dose (RP2D). Read More

Clin Breast Cancer 2018 Nov 22. Epub 2018 Nov 22.

Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom. Electronic address:

Introduction: Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy.

Patients And Methods: Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55. Read More

Dalton Trans 2018 Dec 3. Epub 2018 Dec 3.

University of Puerto Rico, Department of Chemistry, PO Box 9019, Mayagüez, PR 00681, Puerto Rico.

Previously, ferrocene incorporation into the principal structural component of biologically active molecules resulted in enhanced cytotoxic activity against hormone-dependent MCF-7 and T-47D and hormone-independent MDA-MB-231 breast-cancer cell lines. Here we explore 4 new ferrocene estrogen conjugates at position 16 of the estrogen hormone and compared them to the previously reported ferrocene estrogen conjugate 3-ferrocenyl-estra-1,3,5(10)-triene-17β-ol. The ferrocene conjugate 16-ferrocenylidene-3-hydroxyestra-1,3,5(10)-trien-17-one was synthesized using estrone and ferrocene carboxaldehyde as starting materials in 86% yield. Read More

Gland Surg 2018 Oct;7(5):449-457

Breast and Endocrine Surgery Unit, Royal Adelaide Hospital, Adelaide, Australia.

Background: The risk of hormone positive breast cancer extends beyond 5 years. Extended duration of tamoxifen to 10 years has been shown to improve overall survival (OS) and disease-free survival (DFS). In post-menopausal women aromatase inhibitor (AI) is the gold standard for adjuvant endocrine therapy. Read More

Toxicol Appl Pharmacol 2018 Nov 29;363:88-97. Epub 2018 Nov 29.

UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, University of Porto, Porto, Portugal.

The endometrium is a particular sensitive target tissue for estradiol that is able to promptly modify its structure. Tamoxifen (TAM), a selective estrogen receptor modulator, was shown to promote a spectrum of uterine abnormalities, though the morphological and stereological effects of this drug in uterus is not clear. In this way, we have used an established model of ovariectomy followed by estradiol benzoate (EB) or TAM treatment and analyzed their effects in uterine histopathology and proliferation. Read More

Gynecol Oncol 2018 Nov 27. Epub 2018 Nov 27.

Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK. Electronic address:

Objectives: The role of endocrine therapy (ET) in high grade serous ovarian carcinoma (HGSOC) is poorly defined due to the lack of phase III data and significant heterogeneity of clinical trials performed. In this study, we sought to identify predictive factors of endocrine sensitivity in HGSOC.

Methods: HGSOC patients who received at least four weeks of ET for relapsed disease following one line of chemotherapy at the Edinburgh Cancer Centre were identified. Read More

Chem Cent J 2018 Dec 4;12(1):130. Epub 2018 Dec 4.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

Background: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities. Read More

J Cancer Res Clin Oncol 2018 Dec 4. Epub 2018 Dec 4.

Department of Clinical and Experimental Medicine, Department of Oncology, Linköping University, 58185, Linköping, Sweden.

Purpose: The protein tyrosine phosphatase, non-receptor type 2 (PTNP2) regulates receptor tyrosine kinase signalling, preventing downstream activation of intracellular pathways like the PI3K/Akt pathway. The gene encoding the protein is located on chromosome 18p11; the 18p region is commonly deleted in breast cancer. In this study, we aimed to evaluate PTPN2 protein expression in a large breast cancer cohort, its possible associations to PTPN2 gene copy loss, Akt activation, and the potential use as a clinical marker in breast cancer. Read More

Aging (Albany NY) 2018 Dec 4. Epub 2018 Dec 4.

Department of Urology, Shanghai Changzheng Hospital, Shanghai 200003, China.

Long non-coding RNAs (lncRNAs) have been found essential for tumorigenesis of prostate cancer (PC), but its role in the regulation of castration-resistant prostate cancer (CRPC) is poorly identified. Here, we showed that a lncRNA, Breast-Cancer Anti-Estrogen Resistance 4 (BCAR4), which plays a pivotal role in the tamoxifen-resistance of breast cancer, was significantly upregulated in CRPC, but not in castration-sensitive prostate cancer (CSPC), compared to normal prostate tissue. High BCAR4 levels in CRPC were correlated with poor patients' overall survival. Read More

Osteoarthritis Cartilage 2018 Dec 1. Epub 2018 Dec 1.

Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. Electronic address:

Objective: We earlier identified that the histone methyltransferase DOT1L is as a master protector of cartilage health via limiting excessive activation of the Wnt pathway. However, cartilage-specific homozygous Dot1l knockout mice exhibited a severe growth phenotype and perinatal death, which hampered their use in induced or ageing models of osteoarthritis (OA). The aim of this study was to generate and examine haploinsufficient and inducible conditional Dot1l-deficient mouse models to evaluate the importance of DOT1L during post-traumatic or ageing-associated OA onset and progression. Read More

Geriatr Gerontol Int 2018 Dec 3. Epub 2018 Dec 3.

College of Medicine, China Medical University, Taichung, Taiwan.

Aim: This study aimed to evaluate the association between tamoxifen use and hip fractures in older women with breast cancer in Taiwan.

Methods: We carried out a retrospective nationwide case-control study using the database of the Taiwan National Health Insurance Program. A total of 762 female patients with breast cancer aged ≥65 years newly diagnosed with hip fractures from 2000 to 2011 were identified for inclusion in the study. Read More

Proc Natl Acad Sci U S A 2018 Dec 3. Epub 2018 Dec 3.

Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI 48109;

Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root-bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Read More

Lancet Oncol 2018 Nov 30. Epub 2018 Nov 30.

NRG Oncology/NSABP, Pittsburgh, PA, USA; Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA.

Background: The optimal duration of extended therapy with aromatase inhibitors in patients with postmenopausal breast cancer is unknown. In the NSABP B-42 study, we aimed to determine whether extended letrozole treatment improves disease-free survival after 5 years of aromatase inhibitor-based therapy in women with postmenopausal breast cancer.

Methods: This randomised, double-blind, placebo-controlled, phase 3 trial was done in 158 centres in the USA, Canada, and Ireland. Read More

Pathol Oncol Res 2018 Nov 29. Epub 2018 Nov 29.

Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, People's Republic of China.

The management of ductal carcinoma in situ (DCIS) with endocrine therapy remains controversial. A meta-analysis was conducted to evaluate the role of endocrine therapy for DCIS with breast conserving surgery (BCS) and radiotherapy (RT). A total of 7 articles with randomized controlled trials were included. Read More

Cell Physiol Biochem 2018 29;51(4):1518-1532. Epub 2018 Nov 29.

Research Institute of Oncology and Hematology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.

Background/aims: Blocking estrogen signaling with endocrine therapies (Tamoxifen or Fulverstrant) is an effective treatment for Estrogen Receptor-α positive (ER+) breast cancer tumours. Unfortunately, development of endocrine therapy resistance (ETR) is a frequent event resulting in disease relapse and decreased overall patient survival. The long noncoding RNA, H19, was previously shown to play a significant role in estrogen-induced proliferation of both normal and malignant ER+ breast epithelial cells. Read More

J Bone Miner Res 2018 Nov 29. Epub 2018 Nov 29.

Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Aging (CHROMETA), KU Leuven, Herestraat 49 PO box 902, 3000 Leuven, Belgium.

Androgens via the androgen receptor (AR) are required for optimal male bone health. The target cell(s) for the effects of androgens on cortical bone remain(s) incompletely understood. In females, estrogen receptor alpha in neurons is a negative regulator of cortical and trabecular bone. Read More

Elife 2018 Nov 29;7. Epub 2018 Nov 29.

Ben May Department for Cancer Research, University of Chicago, Chicago, United States.

Acquired resistance to endocrine therapy remains a significant clinical burden for breast cancer patients. Somatic mutations in the (estrogen receptor alpha (ERα)) gene ligand-binding domain (LBD) represent a recognized mechanism of acquired resistance. Antiestrogens with improved efficacy versus tamoxifen might overcome the resistant phenotype in ER+ breast cancers. Read More

J Cancer Res Ther 2018 Oct-Dec;14(6):1184-1190

Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Introduction: The relation between Behçet's disease (BD) and breast cancer (BC) is unclear. Our purpose is to investigate whether BD has an important effect on BC or vice versa.

Patients And Methods: A total of 12 female BC patients with a diagnosis of BD were identified from a cohort including 5050 BC patients. Read More

Cancer Med 2018 Nov 28. Epub 2018 Nov 28.

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

We hypothesized that endometrial carcinoma (EC) patients with a prior cancer diagnosis, after accounting for EC arising after tamoxifen-treated prior breast carcinoma, are more likely to have an underlying genetic basis. We used information from a population-based study to compare measured risk factors, tumor characteristics, survival, and known mismatch repair (MMR) pathogenic variant status for EC subgroups according to prior diagnosis of cancer (none, breast cancer tamoxifen-treated or not, Lynch Syndrome (LS)-associated cancer). Family history of any cancer was increased for EC cases with prior breast cancer, both tamoxifen treated (P = 0. Read More

J Womens Health (Larchmt) 2018 Nov 28. Epub 2018 Nov 28.

4 Department of Obstetrics and Gynecology, New York University School of Medicine , New York, New York.

Background: The Surveillance, Epidemiology, and End Result (SEER) database shows a variable increase in endometrial cancer incidence over time. The objective of this review was to examine published endometrial cancer rates and potential etiologies.

Methods: Endometrial cancer incidence was obtained from the SEER Program database from 1975 through 2014, and a test for trend in incidence was calculated. Read More

Breast Cancer Res Treat 2018 Nov 26. Epub 2018 Nov 26.

Department of Gynecology and Obstetrics, University Medical Center, Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.

Background: The role of G-protein-coupled estrogen receptor 1 (GPER-1) in the development of tamoxifen resistance in breast cancer is a highly controversial issue. The aim of this study was to determine the expression of GPER-1 in the clinical routine under conditions of endocrine treatment.

Patients And Methods: GPER-1 expression was analyzed in 442 patients with primary invasive breast cancer. Read More

Oncogenesis 2018 Nov 26;7(11):94. Epub 2018 Nov 26.

Department of Oncology, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China.

Cantharidin, one of the active components of mylabris, is believed to have antitumor activity. Cantharidin selectively inhibits protein phosphatase 2A (PP2A), which can repress multiple oncogenic kinases (ERK, JNK, PKC, and NF-κB). Researches in vitro have shown that cantharidin suppresses cell viability and metastasis in pancreatic cancer cells. Read More

J Clin Oncol 2018 Nov 26:JCO1800440. Epub 2018 Nov 26.

Thomas Ruhstaller and Beat Thürlimann, Kantonsspital St Gallen, St Gallen; Christoph Rochlitz, Universitätsspital, Basel; Elena Kralidis, Kantonsspital, Aarau; Khalil Zaman, University Hospital Vaud University Hospital Center, Lausanne; Alan S. Coates, Aron Goldhirsch, and Beat Thürlimann, International Breast Cancer Study Group, Bern, Switzerland; Anita Giobbie-Hurder, Richard D. Gelber, and Meredith M. Regan, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School, Richard D. Gelber, Harvard TH Chan School of Public Health and Frontier Science and Technology Research Foundation, Boston, MA; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Milan; Simon Spazzapan, CRO National Cancer Institute, Aviano; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Lucia Del Mastro, Ospedale Policlinico San Martino, Genoa; Edda Simoncini, ASST Spedali Civili di Brescia, Brescia; Lorenzo Gianni, Ospedale Infermi di Rimini, AUSL della Romagna, Ravenna; Angelo Di Leo, Hospital of Prato-AUSL Toscana Centro, Prato, Italy; Maj-Britt Jensen and Bent Ejlertsen, Rigshospitalet, Copenhagen; Erik Hugger Jakobsen, Lillebaelt Hospital, Vejle, Denmark; Evandro de Azambuja and Martine Piccart-Gebhart, Institut Jules Bordet and L'Université Libre de Bruxelles, Brussels; Patrick Neven, KU Leuven, Leuven, Belgium; István Láng, National Institute of Oncology, Budapest, Hungary; Laurence Gladieff, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse; Hervé Bonnefoi, Université de Bordeaux, Bordeaux; Corinne Veyret, Centre de Cancérolgie Henri Becquerel, Rouen, France; Vernon J. Harvey, Auckland City Hospital, Auckland, New Zealand; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; and Alan S. Coates, University of Sydney, Sydney, New South Wales, Australia.

Purpose: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Read More

Methods Mol Biol 2019 ;1896:83-92

MRC London Institute of Medical Sciences (LMS), London, UK.

Oncogene-induced senescence (OIS) is a cellular response that limits the replication of cells expressing oncogenes. As a result, OIS is a potent tumor suppressor mechanism limiting cancer progression. Here we describe IMR90 ER:RAS, a widely used model to study OIS in cell culture. Read More

Environ Sci Pollut Res Int 2018 Nov 22. Epub 2018 Nov 22.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.

Selective estrogen receptor modulators such as tamoxifen (TAM) significantly reduce the risks of developing estrogen receptor-positive (ER+) breast cancer. Low concentrations (nanomolar range) of bisphenol A (BPA) shows estrogenic effects and further promotes the proliferation of hormone-dependent breast cancer cells. However, whether or not BPA can influence TAM-treatment resistance in breast cancer has not drawn much attention. Read More

Cancer Prev Res (Phila) 2018 Dec 20;11(12):831-840. Epub 2018 Nov 20.

Department of Surgery, Chemoprevention Center, University of Alabama at Birmingham, Birmingham, Alabama.

To determine the effects of diet, rats were placed on a standard diet (4% fat) or on a modified Western (high-fat diet, HFD) diet (21% fat) at 43 days of age (DOA) and administered methylnitrosourea (MNU) at 50 DOA. Rats were administered effective (tamoxifen, vorozole, and Targretin) or ineffective (metformin and Lipitor) chemopreventive agents either by daily gavage or in the diet beginning at 57 DOA and continuing until sacrifice (190 DOA). Latency period of the tumors was determined by palpation, and multiplicity and cancer weights per rat were determined at final sacrifice. Read More

Breast Cancer Res 2018 Nov 20;20(1):139. Epub 2018 Nov 20.

Clinic of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany.

Background: The sensitivity of estrogen receptor-positive breast cancers to tamoxifen treatment varies considerably, and the molecular mechanisms affecting the response rates are manifold. The human epidermal growth factor receptor-related receptor HER2 is known to trigger intracellular signaling cascades that modulate the activity of coregulators of the estrogen receptor which, in turn, reduces the cell sensitivity to tamoxifen treatment. However, the impact of HER2-related receptor tyrosine kinases HER1, HER3, and, in particular, HER4 on endocrine treatment is largely unknown. Read More

Acta Oncol 2018 Nov 20:1-7. Epub 2018 Nov 20.

a Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Adjuvant tamoxifen therapy approximately halves the risk of recurrence in estrogen receptor-positive (ER+) breast cancer patients, but many women respond insufficiently to therapy. Expression of multi-drug resistance protein 2 (MRP2) in breast cancer may potentiate tamoxifen resistance. Thus, we investigated the expression of MRP2 in breast cancer as a predictor of tamoxifen therapy effectiveness. Read More

NPJ Breast Cancer 2018 14;4:37. Epub 2018 Nov 14.

NRG Oncology/NSABP (NSABP Legacy trials are now part of the NRG Oncology portfolio), Pittsburgh, PA USA.

The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS algorithm with a positive coefficient and contributes to higher RS values. Accrual to B-20 occurred prior to routine testing for HER2, so questions have arisen regarding assay performance if HER2-positive patients were identified and excluded. Read More

Brain Behav Immun 2018 Nov 16. Epub 2018 Nov 16.

Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT Manchester, UK. Electronic address:

The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed () mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1) mice. Read More

Nat Commun 2018 11 19;9(1):4848. Epub 2018 Nov 19.

Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland.

X-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Read More

Nat Commun 2018 11 19;9(1):4849. Epub 2018 Nov 19.

Program for Genetics and Genome Biology, Hospital for Sick Children, 686 Bay Street, Toronto, ON, CAN M5G 0A4, Canada.

Myotubular myopathy (MTM) is a severe X-linked disease without existing therapies. Here, we show that tamoxifen ameliorates MTM-related histopathological and functional abnormalities in mice, and nearly doubles survival. The beneficial effects of tamoxifen are mediated primarily via estrogen receptor signaling, as demonstrated through in vitro studies and in vivo phenotypic rescue with estradiol. Read More

J Cell Mol Med 2018 Nov 18. Epub 2018 Nov 18.

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Tamoxifen (TAM) is a primary drug for treatment of estrogen receptor positive breast cancer. However, TAM resistance remains a serious threat to breast cancer patients and may be attributed to increased stemness of breast cancer. Here, we show that discs large homolog 5 (DLG5) expression is down-regulated in TAM-resistant breast cancer and cells. Read More