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John M S Bartlett, Ikhlaaq Ahmed, Meredith M Regan, Ivana Sestak, Elizabeth A Mallon, Patrizia Dell'Orto, Beat Thürlimann, Caroline Seynaeve, Hein Putter, Cornelis J H Van de Velde, Cassandra L Brookes, John F Forbes, Giuseppe Viale, Jack Cuzick, Mitchell Dowsett, Daniel W Rea
BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. METHODS: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs...
July 2017: European Journal of Cancer
Marcel Jinih, Norma Relihan, Mark A Corrigan, Seamus O'Reilly, Henry P Redmond
The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment...
November 2017: Breast Journal
Charlotte Fribbens, Ben O'Leary, Lucy Kilburn, Sarah Hrebien, Isaac Garcia-Murillas, Matthew Beaney, Massimo Cristofanilli, Fabrice Andre, Sherene Loi, Sibylle Loibl, John Jiang, Cynthia Huang Bartlett, Maria Koehler, Mitch Dowsett, Judith M Bliss, Stephen R D Johnston, Nicholas C Turner
PURPOSE: ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. MATERIALS AND METHODS: In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Kirsten A Nyrop, Leigh F Callahan, Christine Rini, Mary Altpeter, Betsy Hackney, Amy DePue, Anne Wilson, Arielle Schechter, Hyman B Muss
PURPOSE: Breast cancer survivors on aromatase inhibitors (AI) often experience side effects of joint pain, stiffness, or achiness (arthralgia). This study presents findings from a qualitative study of survivors on an AI regarding their knowledge of potential joint pain side effects and how both AI side effects and their management through moderate physical activity could be discussed during routine visits with their oncology provider. METHODS: Qualitative data from semi-structured interviews were content analyzed for emergent themes...
June 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
John M S Bartlett, Jason Christiansen, Mark Gustavson, David L Rimm, Tammy Piper, Cornelis J H van de Velde, Annette Hasenburg, Dirk G Kieback, Hein Putter, Christos J Markopoulos, Luc Y Dirix, Caroline Seynaeve, Daniel W Rea
CONTEXT: Hormone receptors HER2/neu and Ki-67 are markers of residual risk in early breast cancer. An algorithm (IHC4) combining these markers may provide additional information on residual risk of recurrence in patients treated with hormone therapy. OBJECTIVE: To independently validate the IHC4 algorithm in the multinational Tamoxifen Versus Exemestane Adjuvant Multicenter Trial (TEAM) cohort, originally developed on the trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination Trial) cohort, by comparing 2 methodologies...
January 2016: Archives of Pathology & Laboratory Medicine
R T Chlebowski, R Haque, H Hedlin, N Col, E Paskett, J E Manson, J T Kubo, K C Johnson, J Wactawski-Wende, K Pan, G Anderson
In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative...
December 2015: Breast Cancer Research and Treatment
Mohammad Saiful Islam, Gavin Wright, Peter Tanner, Robert Lucas
An otherwise asymptomatic 66-year-old British Caucasian female with a history of breast cancer was referred by the oncologists due to progressively abnormal liver function tests (LFTs). After undergoing wide local excision and axillary dissection she was started on the anti-oestrogen drug Arimidex (anastrozole) as the tumour cells were oestrogen receptor positive. With a background of normal LFTs, an absence of risk factors for chronic liver disease and otherwise good health, 6 months after starting Arimidex the oncology team noted deranged LFTs...
October 2014: Clinical Journal of Gastroenterology
Mitch Dowsett, Ivana Sestak, Richard Buus, Elena Lopez-Knowles, Elizabeth Mallon, Anthony Howell, John F Forbes, Aman Buzdar, Jack Cuzick
PURPOSE: To identify the individual genes or gene modules that lead to the OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby identify indices of residual risk that may guide selection of patients for extended adjuvant therapy. EXPERIMENTAL DESIGN: We conducted a retrospective assessment of the relationship between (i) the individual genes and gene modules of the Recurrence Score and (ii) early (0-5 years) and late (5-10 years) recurrence rates in 1,125 postmenopausal patients with primary estrogen receptor-positive breast cancer treated with anastrozole or tamoxifen in the Arimidex, Tamoxifen, Alone or Combined (ATAC) randomized clinical trial...
June 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ivana Sestak, Jack Cuzick, Mitch Dowsett, Elena Lopez-Knowles, Martin Filipits, Peter Dubsky, John Wayne Cowens, Sean Ferree, Carl Schaper, Christian Fesl, Michael Gnant
PURPOSE: We have previously shown that the PAM50-based risk of recurrence (ROR) score is significantly correlated with distant recurrence in both the translational research cohort within the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial (TransATAC) and Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) randomized trials. Here, we focus on the ROR score for predicting distant recurrence after 5 years of follow-up in a combined analysis of these two randomized trials...
March 10, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Wei Tian, Mathieu Latour, Jonathan I Epstein
Endometrial stromal sarcoma (ESS) involving the urinary bladder is very rare, with no prior series reported. We identified 6 cases of low-grade ESS involving the bladder at our institution (1998 to 2013), 5 of them consults. The median age at bladder involvement was 60 years (range, 44 to 77 y). One patient presented with bladder involvement at initial diagnosis of ESS. The remaining 5 cases with bladder involvement presented 7 to 30 years (mean 18 y) after a known diagnosis of ESS (n=2) or after a remote history of hysterectomy with an uncertain diagnosis (n=3)...
July 2014: American Journal of Surgical Pathology
M Topcul, I Cetin, M Ozlem Kolusayin Ozar
PURPOSE: In this study, the antiproliferative effects of the aromatase inhibitor anastrozole (arimidex®) was evaluated on estrogen receptor (ER) positive FM3A cell line originated from C3H mouse mammary carcinoma. METHODS: For this purpose cell kinetic parameters including viability analysis, mitotic index and labelling index were used. Three different doses of anostrozole (D1= 0.01 μM, D2= 0.1μM, D3= 1μM) were applied to cells for 24 h to determine the most effective dose...
October 2013: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Dennis C Sgroi, Ivana Sestak, Jack Cuzick, Yi Zhang, Catherine A Schnabel, Brock Schroeder, Mark G Erlander, Anita Dunbier, Kally Sidhu, Elena Lopez-Knowles, Paul E Goss, Mitch Dowsett
BACKGROUND: Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial...
October 2013: Lancet Oncology
Kamal M Dawood
INTRODUCTION: Benzofuran moiety constitutes the core of several interesting pharmacologically active natural products. Benzofurans are among feasible potent active inhibitors against many diseases, viruses, microbes, fungus and enzymes. Several series of therapeutically important synthetic and naturally occurring benzofuran-containing compounds are reported in this chapter. AREAS COVERED: The current chapter focuses on the recent applications of benzofuran scaffolds and their wide range of biological activities during 1999 - 2012...
September 2013: Expert Opinion on Therapeutic Patents
G von Minckwitz
No abstract text is available yet for this article.
December 2002: Onkologie
Chiara Ghimenti, Maurizia Mello-Grand, Lea Regolo, Alberto Zambelli, Giovanna Chiorino
Aromatase inhibitors, such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients treated with anastrozole do not respond, and it remains impossible to accurately predict sensitivity. Thus, novel markers to predict response are required. The K303R estrogen receptor (ER)α mutation confers resistance to tamoxifen treatment. Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression vector and stimulated with androstenedione (an aromatase substrate), were found to be resistant to the inhibitory effect of anastrozole...
2010: Experimental and Therapeutic Medicine
Stella Williams, Benedict Michael, Devesh Mewar, Edward Tunn
We report the case of a 51-year-old woman who presented with an inflammatory flare of osteoarthritis of the small joints of her hands occurring in a temporal relationship with the commencement of Arimidex, prescribed to reduce systemic oestrogen levels to treat breast cancer. Following the cessation of Arimidex and the initiation of tamoxifen, a specific oestrogen receptor antagonist, this flare resolved. It has long been observed that during the menopause, as oestrogen levels decline, many women develop osteoarthritis or experience progression of the disease...
2010: BMJ Case Reports
Michael P Lux, Claudia Reichelt, Jon Karnon, Thorsten D Tänzer, Dragan Radosavac, Peter A Fasching, Matthias W Beckmann, Falk C Thiel
BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors (AIs), but the results are inconsistent and disease-free survival has often been extrapolated to overall survival. The present study calculates the cost-effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the context of the German health care system, using survival data from the Breast International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study and generic prices. MATERIALS AND METHODS: A hybrid model was developed that incorporates recurrence rates, overall survival, treatment costs and treatment-associated adverse events and the resulting costs...
October 2011: Breast Care
Christos Markopoulos, Evagelos Tzoracoleftherakis, Dimitrios Koukouras, Basileios Venizelos, Vasilios Zobolas, John Misitzis, Grigorios Xepapadakis, Helen Gogas
PURPOSE: We investigated whether age at anastrozole (A) initiation influences the effect of treatment on bone mineral density (BMD). We conducted a post hoc analysis of the dataset of Arimidex Bone Mass Index Oral Bisphosphonates prospective trial, studying the effect of risedronate (R) on BMD of postmenopausal, early breast cancer patients receiving A. METHODS: Patients were stratified into those with normal BMD or mild osteopenia (T > -2) receiving A-only and patients with mild or severe osteopenia (T ≤ -2) or osteoporosis (T < -2...
September 2012: Journal of Cancer Research and Clinical Oncology
Katja Lundgren, Matthew Brown, Silvia Pineda, Jack Cuzick, Janine Salter, Lila Zabaglo, Anthony Howell, Mitch Dowsett, Göran Landberg
INTRODUCTION: Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen. METHODS: To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial...
2012: Breast Cancer Research: BCR
James M Rae, Suzy Drury, Daniel F Hayes, Vered Stearns, Jacklyn N Thibert, Ben P Haynes, Janine Salter, Ivana Sestak, Jack Cuzick, Mitch Dowsett
BACKGROUND: Adjuvant tamoxifen therapy substantially decreases the risk of recurrence and mortality in women with hormone (estrogen and/or progesterone) receptor-positive breast cancer. Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy. METHODS: Tumor specimens from a subset of postmenopausal patients with hormone receptor-positive early-stage (stages I, II, and IIIA) breast cancer, who were enrolled in the randomized double-blind Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial, were genotyped for variants in CYP2D6 (N = 1203 patients: anastrozole [trade name: Arimidex] group, n = 615 patients; tamoxifen group, n = 588 patients) and UDP-glucuronosyltransferase-2B7 (UGT2B7), whose gene product inactivates endoxifen (N = 1209 patients; anastrozole group, n = 606 patients; tamoxifen group, n = 603 patients)...
March 21, 2012: Journal of the National Cancer Institute
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