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https://www.readbyqxmd.com/read/29162134/serum-thymidine-kinase-1-activity-as-a-pharmacodynamic-marker-of-cyclin-dependent-kinase-4-6-inhibition-in-patients-with-early-stage-breast-cancer-receiving-neoadjuvant-palbociclib
#1
Nusayba Bagegni, Shana Thomas, Ning Liu, Jingqin Luo, Jeremy Hoog, Donald W Northfelt, Matthew P Goetz, Andres Forero, Mattias Bergqvist, Jakob Karen, Magnus Neumüller, Edward M Suh, Zhanfang Guo, Kiran Vij, Souzan Sanati, Matthew Ellis, Cynthia X Ma
BACKGROUND: Thymidine kinase 1 (TK1) is a cell cycle-regulated enzyme with peak expression in the S phase during DNA synthesis, and it is an attractive biomarker of cell proliferation. Serum TK1 activity has demonstrated prognostic value in patients with early-stage breast cancer. Because cyclin-dependent kinase 4/6 (CDK4/6) inhibitors prevent G1/S transition, we hypothesized that serum TK1 could be a biomarker for CDK4/6 inhibitors. We examined the drug-induced change in serum TK1 as well as its correlation with change in tumor Ki-67 levels in patients enrolled in the NeoPalAna trial (ClinicalTrials...
November 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29137842/comparison-of-pharmacokinetics-of-newly-discovered-aromatase-inhibitors-by-a-cassette-microdosing-approach-in-healthy-japanese-subjects
#2
Hiroyuki Kusuhara, Tadayuki Takashima, Hisako Fujii, Tsutomu Takashima, Masaaki Tanaka, Akira Ishii, Shusaku Tazawa, Kazuhiro Takahashi, Kayo Takahashi, Hidekichi Tokai, Tsuneo Yano, Makoto Kataoka, Akihiro Inano, Suguru Yoshida, Takamitsu Hosoya, Yuichi Sugiyama, Shinji Yamashita, Taisuke Hojo, Yasuyoshi Watanabe
The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16...
September 21, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29128813/effect-of-aromatase-inhibitors-on-learning-and-memory-and-modulation-of-hippocampal-dickkopf-1-and-sclerostin-in-female-mice
#3
Saima Zameer, Divya Vohora
BACKGROUND: There has been conflicting reports on the effect of third generation aromatase inhibitors on cognition in estrogen-deficient states. Since aromatase inhibitors themselves cause estrogen deprivation, the present work was designed to evaluate the comparative effect of three aromatase inhibitors on behavioral measures of learning and memory in female mice. Further, in view of the reports of estrogen and Wnt signaling pathway in cognition, the role of two Wnt signaling antagonists (dickkopf-1 and sclerostin) in mediation of cognitive effects of aromatase inhibitors was evaluated...
June 13, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29128193/vitamin-d-levels-vitamin-d-receptor-polymorphisms-and-inflammatory-cytokines-in-aromatase-inhibitor-induced-arthralgias-an-analysis-of-cctg-ma-27
#4
Polly Niravath, Bingshu Chen, Judy-Anne W Chapman, Sandeep K Agarwal, Robert L Welschhans, Tim Bongartz, Krishna R Kalari, Lois E Shepherd, John Bartlett, Kathleen Pritchard, Karen Gelmon, Susan G Hilsenbeck, Mothaffar F Rimawi, C Kent Osborne, Paul E Goss, James N Ingle
BACKGROUND: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. PATIENTS AND METHODS: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation...
October 16, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29126161/early-participant-reported-symptoms-as-predictors-of-adherence-to-anastrozole-in-the-international-breast-cancer-intervention-studies-ii
#5
I Sestak, S G Smith, A Howell, J F Forbes, J Cuzick
Background: Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS) II prevention and Ductal Carcinoma in Situ (DCIS) trials, and its association with early symptoms. Patients and methods: In the prevention trial, 3864 postmenopausal women were randomized to placebo vs. anastrozole. 2980 postmenopausal women with DCIS were randomized to tamoxifen vs...
November 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29108304/evaluating-the-efficacy-of-post-surgery-adjuvant-therapies-used-for-ductal-carcinoma-in-situ-patients-a-network-meta-analysis
#6
Li Wang, Yaoxiong Xia, Dequan Liu, Yueqin Zeng, Li Chang, Lan Li, Yu Hou, Lv Ge, Wenhui Li, Zhijie Liu
Objective: Post-surgery adjuvant therapies are very important for patients suffering from ductal carcinoma in situ (DCIS). In this study we conducted a network meta-analysis (NMA) to evaluate the efficacy of different post-surgery adjuvant therapies including tamoxifen, anastrozole and radiation therapy (RT) and their combinations (RT+ tamoxifen and RT+ anastrozole). Methods: We searched several databases, including Embase, MEDLINE / PUBMED, Cochrane Library, and Science Citation Index, for relevant studies...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29071118/influence-of-aromatase-inhibitors-therapy-on-the-occurrence-of-rheumatoid-arthritis-in-women-with-breast-cancer-results-from-a-large-population-based-study-of-the-italian-society-for-rheumatology
#7
Marta Caprioli, Greta Carrara, Garifallia Sakellariou, Ettore Silvagni, Carlo Alberto Scirè
OBJECTIVES: The purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with tamoxifen. METHODS: Data were collected from the administrative healthcare database of Lombardy Region, Italy, from 2004 to 2013. This study follows a nested cohort design, including women with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole, exemestane or letrozole...
2017: RMD Open
https://www.readbyqxmd.com/read/29031778/extended-adjuvant-aromatase-inhibition-after-sequential-endocrine-therapy-data-a-randomised-phase-3-trial
#8
Vivianne C G Tjan-Heijnen, Irene E G van Hellemond, Petronella G M Peer, Astrid C P Swinkels, Carolien H Smorenburg, Maurice J C van der Sangen, Judith R Kroep, Hiltje De Graaf, Aafke H Honkoop, Frans L G Erdkamp, Franchette W P J van den Berkmortel, Maaike de Boer, Wilfred K de Roos, Sabine C Linn, Alexander L T Imholz, Caroline M Seynaeve
BACKGROUND: The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen. METHODS: DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands...
October 11, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28977209/the-use-of-aromatase-inhibitors-in-boys-with-short-stature-what-to-know-before-prescribing
#9
REVIEW
Alessandra Linardi, Durval Damiani, Carlos A Longui
Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs...
July 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28968163/monarch-3-abemaciclib-as-initial-therapy-for-advanced-breast-cancer
#10
RANDOMIZED CONTROLLED TRIAL
Matthew P Goetz, Masakazu Toi, Mario Campone, Joohyuk Sohn, Shani Paluch-Shimon, Jens Huober, In Hae Park, Olivier Trédan, Shin-Cheh Chen, Luis Manso, Orit C Freedman, Georgina Garnica Jaliffe, Tammy Forrester, Martin Frenzel, Susana Barriga, Ian C Smith, Nawel Bourayou, Angelo Di Leo
Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting...
November 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28955236/improvement-of-bone-physiology-and-life-quality-due-to-association-of-risedronate-and-anastrozole
#11
Vincenzo Monda, Gelsy A Lupoli, Giovanni Messina, Rosario Peluso, Annalisa Panico, Ines Villano, Monica Salerno, Francesco Sessa, Francesca Marciello, Fiorenzo Moscatelli, Anna Valenzano, Leonardo Molino, Roberta Lupoli, Francesco Fonderico, Anna Tortora, Agata Pisano, Maria Ruberto, Marsala Gabriella, Gina Cavaliere, Giovanna Trinchese, Maria P Mollica, Luigi Cipolloni, Giuseppe Cibelli, Marcellino Monda, Giovanni Lupoli, Antonietta Messina
The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28943895/assessment-of-bone-metabolism-and-biomechanical-properties-of-the-femur-following-treatment-with-anastrozole-and-letrozole-in-an-experimental-model-of-menopause
#12
Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, Laskarina-Maria Korou, Athanasios Mitousoudis, Emmanouil Kalampokas, Efthimios Deligeoroglou, Odysseas Gregoriou, Despina N Perrea, George Creatsas, Stavros Kourkoulis
The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28935854/comparison-of-helical-tomotherapy-and-direct-tomotherapy-in-bilateral-whole-breast-irradiation-in-a-case-of-bilateral-synchronous-grade-1-and-stage-1-breast-cancer
#13
Valentina Lancellotta, Martina Iacco, Elisabetta Perrucci, Claudio Zucchetti, Anna Concetta Dipilato, Lorenzo Falcinelli, Isabella Palumbo, Cynthia Aristei
BACKGROUND Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. CASE REPORT A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative)...
September 22, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28926141/working-at-the-membrane-interface-ligand-induced-changes-in-dynamic-conformation-and-oligomeric-structure-in-human-aromatase
#14
Giovanna Di Nardo, Giuseppe Cimicata, Roberta Baravalle, Valentina Dell'Angelo, Alberto Ciaramella, Gianluca Catucci, Piero Ugliengo, Gianfranco Gilardi
Aromatase catalyzes the biosynthesis of estrogens from androgens. Owing to the physiological importance of this conversion of lipophilic substrates, the interaction with the lipid bilayer for this cytochrome P450 is crucial for its dynamics that must allow an easy access to substrates and inhibitors. Here, the aromatase-anastrozole interaction is studied by combining computational methods to identify possible access/egress routes with the protein inserted in the membrane and experimental tools aimed at the investigation of the effect of the inhibitor on the protein conformation...
September 19, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28906164/comparative-pharmacokinetics-study-of-anastrozole-after-single-administration-and-combination-with-celecoxib
#15
Xiaoyang Sun, Mingming Lv, Binjie Wang, Simin Zhao, Ping Guo, Shixiao Wang, Liqiang Gu, Xiaohui Chen
1. There are numerous investigations demonstrating that the cyclooxygenase-2 (COX-2) inhibitors might enhance the efficiency of anastrozole in breast cancer. Hence, this study was conducted to investigate the comparative pharmacokinetics of anastrozole after single administration and combination with celecoxib. 2. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recovery for both anastrozole and the internal standard, and then anastrozole was separated and analysed on an ACQUITY BEH UPLC C18 column (50 × 2...
September 14, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28874413/a-phase-ii-trial-of-neoadjuvant-mk-2206-an-akt-inhibitor-with-anastrozole-in-clinical-stage-ii-or-iii-pik3ca-mutant-er-positive-and-her2-negative-breast-cancer
#16
Cynthia X Ma, Vera Suman, Matthew P Goetz, Donald Northfelt, Mark E Burkard, Foluso Ademuyiwa, Michael Naughton, Julie Margenthaler, Rebecca Aft, Richard Gray, Amye Tevaarwerk, Lee Wilke, Tufia Haddad, Timothy Moynihan, Charles Loprinzi, Tina Hieken, Erica K Barnell, Zachary L Skidmore, Yan-Yang Feng, Kilannin Krysiak, Jeremy Hoog, Zhanfang Guo, Leslie Nehring, Kari B Wisinski, Elaine Mardis, Ian S Hagemann, Kiran Vij, Souzan Sanati, Hussam Al-Kateb, Obi L Griffith, Malachi Griffith, Laurence Doyle, Charles Erlichman, Matthew J Ellis
Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER(+)) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA-mutant ER(+) breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER(+) breast cancer.Experimental Design: Potential eligible patients with clinical stage II/III ER(+)/HER2(-) breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing...
September 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28862117/hormone-therapy-in-breast-cancer
#17
Mădălina Drăgănescu, Codruţa Carmocan
Hormonal therapy is mandatory for all patients with hormonereceptor- positive breast neoplasms. It is active both in adjuvant and metastatic disease. The only active adjuvant hormonal therapy in pre- and postmenopause is Tamoxifen. The adjuvant treatment duration influences disease-free survival, the risk of a contralateral breast cancer apparition and overall survival. The aromatase inhibitors: Anastrozol, Letrozol, Exemestan are only used in postmenopause. Fulvestrant is used in recurrent disease after or during treatment with Tamoxifen...
July 2017: Chirurgia
https://www.readbyqxmd.com/read/28859291/relevance-of-spatial-heterogeneity-of-immune-infiltration-for-predicting-risk-of-recurrence-after-endocrine-therapy-of-er-breast-cancer
#18
Andreas Heindl, Ivana Sestak, Kalnisha Naidoo, Jack Cuzick, Mitchell Dowsett, Yinyin Yuan
Background: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28859208/height-increment-and-laboratory-profile-of-boys-treated-with-aromatase-inhibitors-with-or-without-growth-hormone
#19
Ludmila Fernandes Pedrosa, Joice Marquez de Oliveira, Paula Roberta Vieira Thomé, Cristiane Kochi, Durval Damiani, Carlos Alberto Longui
Aromatase inhibitors (AIs) have been used to recover height loss due to their capacity to delay growth plate closure. Long-term studies describing final heights are needed to determine the efficacy and safety profiles of these drugs for the treatment of impaired growth. This study aims to identify the therapeutic efficiency of AIs in improve growth and to describe potential adverse effects during treatment. Retrospective data analysis of 96 adolescents, among which 22 patients already attained near-final height, were followed at outpatient clinics of two referral centers...
October 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28852601/solitary-orbital-metastasis-35-years-after-a-diagnosis-of-lobular-carcinoma-in-situ
#20
Matthew B Spraker, Courtney E Francis, Larissa Korde, Janice Kim, Lia Halasz
This report describes a solitary orbital metastasis of lobular carcinoma in a woman 35 years after diagnosis of right breast lobular carcinoma in situ (LCIS). After partial response to anastrozole, the patient was treated with proton radiotherapy to 45 cobalt gray equivalents (CGE) with an excellent response. We additionally discuss treatment strategies for this rare metastatic site.
June 28, 2017: Curēus
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