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https://www.readbyqxmd.com/read/29202611/aurora-kinase-a-as-a-possible-marker-for-endocrine-resistance-in-early-estrogen-receptor-positive-breast-cancer
#1
Anne E Lykkesfeldt, Benedikte R Iversen, Maj-Britt Jensen, Bent Ejlertsen, Anita Giobbie-Hurder, Birgit E Reiter, Tove Kirkegaard, Birgitte B Rasmussen
BACKGROUND: Cell culture studies have disclosed that the mitotic Aurora kinase A is causally involved in both tamoxifen and aromatase inhibitor resistant cell growth and thus may be a potential new marker for endocrine resistance in the clinical setting. MATERIAL AND METHODS: Archival tumor tissue was available from 1323 Danish patients with estrogen receptor (ER) positive primary breast cancer, who participated in the Breast International Group (BIG) 1-98 trial, comparing treatment with tamoxifen and letrozole and both in a sequence...
December 4, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29202405/potent-aromatase-inhibitors-and-molecular-mechanism-of-inhibitory-action
#2
Hongjun Kang, Xingqing Xiao, Chao Huang, Yan Yuan, Dongyan Tang, Xiaochang Dai, Xianghui Zeng
Estrogen is a significant factor in the maintenance and progression of hormone-dependent breast cancer. As well known, aromatase mediates the production of estrogen. Thus, inhibition of aromatase with chemical molecules has been considered to be an effective treatment for estrogen receptor-positive (ER+) breast cancer. In this work, we designed and synthesized a series of novel non-steroidal molecules containing 2-phenylindole scaffold and moiety of either imidazole or 1,2,4-triazole to enhance their binding capacity with the aromatase...
November 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29196963/serum-lipid-and-bone-metabolism-effects-of-toremifene-vs-letrozole-as-adjuvant-therapy-for-postmenopausal-early-breast-cancer-patients-results-of-a-multicenter-open-randomized-study
#3
Tadahiko Shien, Hiroyoshi Doihara, Nobuaki Sato, Keisei Anan, Kansei Komaki, Keisuke Miyauchi, Yasuhiro Yanagita, Tomomi Fujisawa, Shoshu Mitsuyama, Chizuko Kanbayashi, Mikihiro Kusama, Morihiko Kimura, Hiromitsu Jinno, Muneaki Sano, Tadashi Ikeda
A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2...
December 1, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29196492/high-fat-diet-exposure-from-pre-pubertal-age-induces-pcos-in-rats
#4
Roshni S Patel, Gaurang B Shah
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal models focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high fat diet (HFD)...
December 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29194389/variation-in-cyp2a6-activity-and-personalized-medicine
#5
REVIEW
Julie-Anne Tanner, Rachel F Tyndale
The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine-the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism of nicotine and other CYP2A6 substrates including cotinine, tegafur, letrozole, efavirenz, valproic acid, pilocarpine, artemisinin, artesunate, SM-12502, caffeine, and tyrosol. CYP2A6 expression and activity are also impacted by non-genetic factors, including induction or inhibition by pharmacological, endogenous, and dietary substances, as well as age-related changes, or interactions with other hepatic enzymes, co-enzymes, and co-factors...
December 1, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29177067/joint-symptoms-associated-with-anastrozole-and-letrozole-in-patients-with-breast-cancer-a-retrospective-comparative-study
#6
Yoshihito Morimoto, Shuhei Sarumaru, Yuko Oshima, Chiho Tsuruta, Kazuhiro Watanabe
Background: Joint symptoms are a common side effect of aromatase inhibitors. However, it is not known if the risk of these symptoms varies between the members of this drug class. The aim of this study was to compare the frequency of joint symptoms associated with anastrozole and that associated with letrozole. Methods: We retrospectively reviewed patients with breast cancer who were treated with anastrozole or letrozole at Tsukiji Breast Clinic, Japan, between April 2008 and July 2014...
2017: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/29174128/intrauterine-insemination-with-ovarian-stimulation-versus-expectant-management-for-unexplained-infertility-tui-a-pragmatic-open-label-randomised-controlled-two-centre-trial
#7
Cynthia M Farquhar, Emily Liu, Sarah Armstrong, Nicola Arroll, Sarah Lensen, Julie Brown
BACKGROUND: Women with unexplained infertility are often offered intrauterine insemination (IUI) with ovarian stimulation as an alternative to in-vitro fertilisation (IVF). However, little evidence exists that IUI is an effective treatment. In 2013, the UK National Institute for Health and Care Excellence recommended that IUI should not be routinely offered for couples with unexplained infertility. METHODS: For this pragmatic, open-label, randomised, controlled, two-centre study, we enrolled women attending two fertility clinics in New Zealand with unexplained infertility and an unfavourable prognosis of natural conception...
November 23, 2017: Lancet
https://www.readbyqxmd.com/read/29169010/oxidative-stress-burden-inhibits-spermatogenesis-in-adult-male-rats-testosterone-protective-effect
#8
Samy Makary, Mohamed Abdo, Ereny Fekry
In this study, we aimed to investigate the protective effects of androgens, using letrozole (LET; an aromatase inhibitor), grape seed extract (GSE; a naturally occurring aromatase inhibitor and antioxidant), and testosterone propionate (Tp), against methotrexate (MTX)-induced testicular toxicity in adult male rats. MTX has been shown to induce oxidative stress and exhibit antiproliferative effects in the testes. Adult male rats received oral saline gavage (control group with no treatment), the potential protective agents (LET, GSE, or Tp) alone, MTX alone, or a combination of one of the potential protective agents and MTX...
November 23, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29168427/neoadjuvant-letrozole-for-postmenopausal-estrogen-receptor-positive-her2-negative-breast-cancer-patients-a-study-from-the-danish-breast-cancer-cooperative-group-dbcg
#9
Signe Korsgaard Skriver, Anne-Vibeke Laenkholm, Birgitte Bruun Rasmussen, Jürgen Handler, Bo Grundtmann, Tove Filtenborg Tvedskov, Peer Christiansen, Ann S Knoop, Maj-Britt Jensen, Bent Ejlertsen
INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive surgery...
November 23, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29164421/ribociclib-plus-letrozole-versus-letrozole-alone-in-patients-with-de-novo-hr-her2-advanced-breast-cancer-in-the-randomized-monaleesa-2-trial
#10
Joyce O'Shaughnessy, Katarina Petrakova, Gabe S Sonke, Pierfranco Conte, Carlos L Arteaga, David A Cameron, Lowell L Hart, Cristian Villanueva, Erik Jakobsen, Joseph T Beck, Deborah Lindquist, Farida Souami, Shoubhik Mondal, Caroline Germa, Gabriel N Hortobagyi
PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. METHODS: Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation...
November 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29158285/neoadjuvant-palbociclib-on-er-breast-cancer-n007-clinical-response-and-endopredict-value
#11
Louis Wc Chow, Satoshi Morita, Christopher Yc Chow, Wai Kuen Ng, Masakazu Toi
To test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2cm or greater, were enrolled in an open-label, single arm study. Twenty eligible patients were given letrozole 2.5mg per day together with palbociclib 125mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end-points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI)...
November 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29158011/extended-adjuvant-intermittent-letrozole-versus-continuous-letrozole-in-postmenopausal-women-with-breast-cancer-sole-a-multicentre-open-label-randomised-phase-3-trial
#12
Marco Colleoni, Weixiu Luo, Per Karlsson, Jacquie Chirgwin, Stefan Aebi, Guy Jerusalem, Patrick Neven, Erika Hitre, Marie-Pascale Graas, Edda Simoncini, Claus Kamby, Alastair Thompson, Sibylle Loibl, Joaquín Gavilá, Katsumasa Kuroi, Christian Marth, Bettina Müller, Seamus O'Reilly, Vincenzo Di Lauro, Andrea Gombos, Thomas Ruhstaller, Harold Burstein, Karin Ribi, Jürg Bernhard, Giuseppe Viale, Rudolf Maibach, Manuela Rabaglio-Poretti, Richard D Gelber, Alan S Coates, Angelo Di Leo, Meredith M Regan, Aron Goldhirsch
BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries...
November 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29158010/complexity-of-intermittent-letrozole-adjuvant-therapy
#13
Rowan T Chlebowski, Kathy Pan
No abstract text is available yet for this article.
November 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29157627/letrozole-may-be-a-valuable-maintenance-treatment-in-high-grade-serous-ovarian-cancer-patients
#14
V Heinzelmann-Schwarz, A Knipprath Mészaros, S Stadlmann, F Jacob, A Schoetzau, K Russell, M Friedlander, G Singer, M Vetter
OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071)...
November 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29154779/letrozole-pre-treatment-prior-to-medical-termination-of-pregnancy-a-systematic-review
#15
Christopher M Nash, Lauren Philp, Prakesh Shah, Kellie E Murphy
OBJECTIVE(S): The purpose of this systematic review was to evaluate the efficacy of pretreatment with letrozole prior to either a first or second trimester medical termination of pregnancy. STUDY DESIGN: We searched letrozole, femara, aromatase inhibitors, abortifacient agents, termination of pregnancy, and labour induction in MEDLINE, EMBASE, Cochrane Database, Google Scholar, and PubMed from inception of each database until September 2015 with no language limitation...
November 14, 2017: Contraception
https://www.readbyqxmd.com/read/29142445/a-study-of-controlled-ovarian-stimulation-with-clomiphene-citrate-or-letrozole-in-combination-with-gonadotropins-and-iui-in-unexplained-infertility
#16
Madhusmita Hembram, Ratna Biswas, Anju Jain
Aim: To compare the effect of clomiphene citrate (CC) + human menopausal gonadotropin (hMG) with letrozole + hMG on size, number of follicles, endometrial thickness, serum levels of oestradiol and progesterone and pregnancy rate. Settings and Design: Non-randomised interventional study. Patients and Methods: A total number of 60 patients in the age group of 20-35 years with unexplained infertility were divided into two groups, 30 in each. Group A received CC + hMG and group B received letrozole + hMG...
July 2017: Journal of Human Reproductive Sciences
https://www.readbyqxmd.com/read/29137418/a-randomized-phase-ii-study-of-aromatase-inhibitors-plus-metformin-in-pre-treated-postmenopausal-patients-with-hormone-receptor-positive-metastatic-breast-cancer
#17
Yannan Zhao, Chengcheng Gong, Zhonghua Wang, Jian Zhang, Leiping Wang, Sheng Zhang, Jun Cao, Zhonghua Tao, Ting Li, Biyun Wang, Xichun Hu
Background: Everolimus significantly improves progression-free survival (PFS) and has been approved to use in aromatase inhibitor pretreated patients with hormone receptor positive advanced breast cancer. Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors. Methods: 60 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer were randomly assigned 1:1 to aromatase inhibitor (exemestane 25mg/d or letrozole 2...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132462/-familial-male-limited-precocious-puberty-due-to-asp578his-mutations-in-the-lhcgr-gene-clinical-characteristics-and-gene-analysis-in-an-infant
#18
Min Wang, Min Li, Yue-Sheng Liu, Si-Min Lei, Yan-Feng Xiao
The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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
#19
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/29125183/ovarian-surgery-for-symptom-relief-in-women-with-polycystic-ovary-syndrome
#20
REVIEW
Sam Lepine, Junyoung Jo, Mostafa Metwally, Ying C Cheong
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting approximately one in 10 women. PCOS is defined by two of three features: oligo- or anovulation, clinical or biochemical hyperandrogenism or both, or polycystic ovaries.Women with PCOS can have a wide range of health problems, including infrequent and irregular periods, unwanted hair growth and acne, and subnormal fertility. Long-term health concerns include an increased risk of heart disease, diabetes and the development of precancerous disease of the womb...
November 10, 2017: Cochrane Database of Systematic Reviews
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