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Aromatase inhibitor

Guillermo Gervasini, Carlos Jara, Clara Olier, Nuria Romero, Ruth Martínez, Juan Antonio Carrillo
AIMS: Anastrozole, an aromatase inhibitor widely used in breast cancer, has recently been pointed out as a P-glycoprotein (ABCB1) substrate. We have aimed to determine whether ABCB1 single-nucleotide polymorphisms (SNPs) can affect anastrozole plasma concentrations in these patients. In addition, we assessed the impact of SNPs in CYP19A1 and TCL1A on the development of arthralgia and cancer recurrence in our series. METHODS: One-hundred-and-ten postmenopausal women with hormone receptor-positive breast cancer were included...
October 17, 2016: British Journal of Clinical Pharmacology
Martine Extermann, Christiaan Leeuwenburgh, Laila Samiian, Marina Sehovic, Jinze Xu, Christopher Cubitt, Paul B Jacobsen, Marco Pahor, Stephen R Grobmyer, Todd M Manini
OBJECTIVE: Chemotherapy is less often prescribed in older individuals due to concerns about post-treatment morbidity and quality of life. We evaluated the physical performance of breast cancer survivors treated with and without adjuvant chemotherapy. MATERIALS AND METHODS: We conducted a case-control study in 56 estrogen receptor positive breast cancer survivors (BCS) on adjuvant aromatase inhibitors 1-2years after definitive surgery. Cases had received adjuvant chemotherapy (n=27; age 70...
October 13, 2016: Journal of Geriatric Oncology
Armando Orlandi, Carmela Di Dio, Maria Alessandra Calegari, Carlo Barone
Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15-3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15-3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth...
October 13, 2016: Biomarkers in Medicine
Kaori Tane, Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Kouhei Akazawa, Yasuo Miyoshi
BACKGROUND: Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs)...
October 12, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Ute Berndt, Bernd Leplow, Robby Schoenfeld, Tilmann Lantzsch, Regina Grosse, Christoph Thomssen
INTRODUCTION: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance. METHODS: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer. Memory and spatial cognition were compared across 4 treatment groups: tamoxifen only (TAM, n = 22), aromatase inhibitor only (AI, n = 22), TAM followed by AI ('SWITCH group', n = 15), and patients with local therapy (LT) only (surgery and radiation, n = 21)...
August 2016: Breast Care
Gretchen L Gierach, Rochelle E Curtis, Ruth M Pfeiffer, Maeve Mullooly, Estelle A Ntowe, Robert N Hoover, Sarah J Nyante, Heather Spencer Feigelson, Andrew G Glass, Amy Berrington de Gonzalez
Importance: Within 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common. Objective: To determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting...
October 6, 2016: JAMA Oncology
Manouk van der Steen, Rolph Pfundt, Stephan J W H Maas, Willie M Bakker-vanWaarde, Roelof J Odink, Anita C S Hokken-Koelega
BACKGROUND: Some children born SGA show advanced bone age (BA) during GH treatment. ACAN-gene mutations have been described in children with idiopathic short stature and advanced BA. OBJECTIVE: To determine presence of ACAN-gene mutations in short SGA children with advanced BA and to assess the response to GH treatment. METHODS: BA assessment in 290 GH-treated SGA children and ACAN-sequencing in 29 children with advanced BA of ≥0.5 years compared to calendar age...
October 6, 2016: Journal of Clinical Endocrinology and Metabolism
Nelly Mauras, Judith L Ross, Priscila Gagliardi, Y Miles Yu, Jobayer Hossain, Joseph Permuy, Ligeia Damaso, Debbie Merinbaum, Ravinder J Singh, Ximena Gaete, Veronica Mericq
CONTEXT: Growth of short children in puberty is limited by estrogen's effect on epiphyseal fusion. OBJECTIVES: To compare: (1) efficacy and safety of aromatase inhibitors (AIs) vs. GH vs. AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and (2) body composition among groups. DESIGN: Randomized 3 arms open-label comparator Setting: Outpatient clinical research Patients: 76 pubertal boys, mean (SE) age: 14...
October 6, 2016: Journal of Clinical Endocrinology and Metabolism
Cláudia de Brito, Margareth Crisóstomo Portela, Mauricio Teixeira Leite de Vasconcellos
Objectives To better understand the role that health care plays in breast cancer survival by investigating the effects that hormone therapy adherence and other select health care variables, adjusted for clinical and sociodemographic factors, had among a population of women in Rio de Janeiro, Brazil. Methods This was a longitudinal study based on secondary data of 5 861 women treated with hormone therapy (tamoxifen or aromatase inhibitors) at the National Cancer Institute of Brazil (INCA), from 1 January 2004 - 29 October 2010...
June 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Edoardo Colzani, Mark Clements, Anna L V Johansson, Annelie Liljegren, Wei He, Judith Brand, Jan Adolfsson, Tommy Fornander, Per Hall, Kamila Czene
BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients...
October 4, 2016: British Journal of Cancer
Gian Mario Tiboni, Adalisa Ponzano
Aromatase inhibitors (AIs) are a class of drugs that act by blocking the production of estrogens from androgens. The current review concentrates on the prenatal developmental toxicity of AIs in experimental models. Available data indicate that AIs may affect pregnancy at human therapeutic or lower doses. The window of vulnerability to AIs is not limited to organogenesis, but also includes the preimplantation stage and fetal periods. Decreased embryo/fetal survival was the prominent treatment-related effect...
September 30, 2016: Reproductive Toxicology
Hatem Abu Hashim
Orally active aromatase inhibitors (AIs) have gained attention for treatment of infertile women with endometriosis in whom aromatase p450 is aberrantly expressed. This review aimed to critically appraise and summarize the available evidence concerning the use of AIs for management of endometriosis-associated infertility. PubMed was searched to May 2015 with the following key words: endometriosis, infertility and aromatase. Priority was given for randomized controlled trials (RCTs) followed by other study designs...
October 2016: International Journal of Fertility & Sterility
Husam Abdel-Qadir, Eitan Amir, Hadas D Fischer, Longdi Fu, Peter C Austin, Paula J Harvey, Paula A Rochon, Douglas S Lee, Geoffrey M Anderson
BACKGROUND: Aromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials. METHODS: Observational population-based cohort study of women aged >55 years diagnosed with stage I-III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI)...
September 29, 2016: European Journal of Cancer
Susanne U Miedlich, Nima Karamooz, Stephen R Hammes
OBJECTIVE: Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e...
September 29, 2016: Bone
Jin Song, Zehui Wu, Phumvadee Wangtrakuldee, Seok Rye Choi, Zhihao Zha, Karl Ploessl, Robert H Mach, Hank F Kung
Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of estrogens. Imaging agents based on aromatase inhibitors (AIs) has been developed for a PET/SPECT study. A series of compounds was synthesized based on YM511, which has previously been used for breast cancer treatment. Two examples of these derivatives, 4-(((4-iodophenyl)methyl)-4H-1,2,4-triazol-4-yl-amino)-benzonitrile (5) and 4-((1H-imidazol-1-yl)(4-iodobenzyl)amino)benzonitrile (11), displayed potent binding affinities to human aromatase (IC50 = 0...
October 2, 2016: Journal of Medicinal Chemistry
Palak Choksi, Margaret E Williams, Kelley M Kidwel, Julia Stella, Mary Soyster, David Hanauer, Catherine Van Poznak
BACKGROUND: Falling increases the risk for fracture. The impact of adjuvant aromatase inhibitors (AI) on the risk of falls is undefined. METHODS: A retrospective case control study was performed examining women with early stage breast cancer on adjuvant AI and matched controls without cancer. Fall and fracture data were abstracted from the medical record. RESULTS: Matched pairs of 332 women were identified (total N = 664). There was no statistically significant difference in the odds of a fall between cases and controls, p = 0...
2016: J Bone Rep Recomm
Jessica F Hoffman, Christopher L Wright, Margaret M McCarthy
UNLABELLED: Identifying and understanding critical periods in brain development is essential to decoding the long-term impact of widespread, poorly defined, and frequently occurring insults such as inflammation. Using the laboratory rat Rattus norvegicus, we have discovered a narrowly constrained critical period in Purkinje neuron development subject to dysregulation by inflammation. The onset and offset of heightened vulnerability are attributed to a tightly orchestrated gene expression profile present only during the second postnatal week and not the first or third weeks...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Suzanne N Landi, Kemi M Doll, Jeannette T Bensen, Laura Hendrix, Carey K Anders, Jennifer M Wu, Hazel B Nichols
PURPOSE: Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. METHODS: Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort...
September 28, 2016: Cancer Causes & Control: CCC
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra N Dwivedi
In the present study, 300 plant derived secondary metabolites (100 each of alkaloid, flavonoid, and terpenoid), have been screened for their anti-cancerous activity through inhibition of selected key enzymatic targets, namely cyclooxygenases (COXs), topoisomerases (Topos), and aromatase by molecular docking approach. Furthermore, the stability of the complexes of top hits, from each class of secondary metabolites, with their respective enzymatic targets was analyzed using molecular dynamics (MD) simulation analyses and binding free energy calculations...
September 25, 2016: Journal of Biomolecular Structure & Dynamics
Miho Kono, Takeo Fujii, Genevieve Ray Lyons, Lei Huo, Roland Bassett, Yun Gong, Meghan Sri Karuturi, Debu Tripathy, Naoto T Ueno
PURPOSE: The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients. METHODS: We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting...
November 2016: Breast Cancer Research and Treatment
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