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Aromatase inhibitors

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https://www.readbyqxmd.com/read/28922787/optimal-duration-of-extended-adjuvant-endocrine-therapy-for-early-breast-cancer-results-of-the-ideal-trial-boog-2006-05
#1
Erik J Blok, Judith R Kroep, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Hein Putter, Joan van den Bosch, Eduard Maartense, A Elise van Leeuwen-Stok, Gerrit-Jan Liefers, Johan W R Nortier, Emiel J Th Rutgers, Cornelis J H van de Velde
Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922781/toxicity-of-extended-adjuvant-therapy-with-aromatase-inhibitors-in-early-breast-cancer-a-systematic-review-and-meta-analysis
#2
Hadar Goldvaser, Tristan A Barnes, Boštjan Šeruga, David W Cescon, Alberto Ocaña, Domen Ribnikar, Eitan Amir
Background: A number of randomized controlled trials (RCTs) have reported improvement in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial five years after diagnosis. However, the toxicity profile of extended AIs is uncertain. Methods: We identified RCTs that compared extended AIs to placebo or no treatment using MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to harm (NNH) were computed for prespecified safety and tolerability outcomes including cardiovascular events, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation for adverse events, and death without recurrence...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28911882/aromatase-inhibitors-a-new-approach-for-controlling-ovarian-function-in-cattle
#3
M J Yapura, E M Zwiefelhofer, R A Pierson, G P Adams
Numerous treatments and protocols have been used to control the reproductive cycle in cattle, with varying effectiveness and many involving the administration of steroid hormones. Steroid hormones, such as estradiol, are perceived as having a negative impact on consumer health. This internationally shared opinion has led to a ban on the use of steroid hormones in food producing animals in many countries (i.e., European Union, New Zealand, and Australia). Letrozole, a non-steroidal aromatase inhibitor, inactivates the aromatase enzyme responsible for the synthesis of estrogens by reversibly binding to the "heme" group of the P450 subunit...
September 11, 2017: Theriogenology
https://www.readbyqxmd.com/read/28911174/sex-reversal-and-comparative-data-undermine-the-w-chromosome-and-support-z-linked-dmrt1-as-the-regulator-of-gonadal-sex-differentiation-in-birds
#4
Claire E Hirst, Andrew T Major, Katie L Ayers, Rosie J Brown, Mylene Mariette, Timothy B Sackton, Craig A Smith
The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF)...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28904441/everolimus-associated-acute-kidney-injury-in-patients-with-metastatic-breast-cancer
#5
A Chandra, N S Rao, K P Malhotra, M Rastogi, R Khurana
Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28894848/risk-reduction-strategies-in-breast-cancer-prevention
#6
REVIEW
Mauricio Costa, Paula Saldanha
Evaluating the risk of breast cancer makes it possible to identify women with a high risk of developing breast cancer in the future. Adopting a healthier lifestyle, involving diet and exercise, is one way of reducing this risk-but there are other, non-modifiable risk factors, such as family history, genetics and diagnosis of premalignant lesions. In this high-risk population, the tracking must be rigorous and involve the participation of the patient herself, earlier and more frequent clinical assessment, and the use of imaging screening...
July 2017: Eur J Breast Health
https://www.readbyqxmd.com/read/28893547/17%C3%AE-estradiol-modulates-cell-proliferation-of-medullary-cords-during-ovarian-differentiation-of-the-lepidochelys-olivacea-sea-turtle
#7
Verónica Díaz-Hernández, Alma Vázquez-Gómez, Alejandro Marmolejo-Valencia, Luis Manuel Montaño, Horacio Merchant-Larios
In turtles undergoing temperature sex determination (TSD), bipotential gonads express Sox9 in medullary cords at both female- (FPT) and male-producing temperatures (MPT). Subsequently, when the sex fate of medullary cords becomes dimorphic, at FPT, Sox9 is downregulated, whereas at MPT, its expression is maintained. Medullary cords in the ovary turn into ovarian lacuna, whereas in the testis they differentiate as seminiferous cords. When embryos of Lepidochelys olivacea sea turtle are incubated at MPT and treated with estradiol, Sox9 expression persists in the medullary cords in the form of tiny ovotestis-like formations...
September 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28889761/safety-issues-associated-with-using-medication-to-treat-overactive-bladder
#8
George Araklitis, Linda Cardozo
The mainstay of overactive bladder treatment is the use of anticholinergic medication with its common side effects well known. This review focused on three less well-known safety issues when treating OAB. Areas covered: Patients with increased anticholinergic load are at risk of cognitive decline, dementia or even death. The elderly are particularly at risk due to polypharmacy. Botulinum toxin carries the risk of high urinary residuals, urinary tract infection and need to self catheterise. The use of vaginal oestrogens may improve OAB symptoms, but there is concern in those with a history of breast cancer...
September 10, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28886606/high-throughput-analysis-of-ovarian-cycle-disruption-by-mixtures-of-aromatase-inhibitors
#9
Frederic Y Bois, Nazanin Golbamaki-Bakhtyari, Simona Kovarich, Cleo Tebby, Henry A Gabb, Emmanuel Lemazurier
BACKGROUND: Combining computational toxicology with ExpoCast exposure estimates and ToxCast™ assay data gives us access to predictions of human health risks stemming from exposures to chemical mixtures. OBJECTIVES: We explored, through mathematical modeling and simulations, the size of potential effects of random mixtures of aromatase inhibitors on the dynamics of women's menstrual cycles. METHODS: We simulated random exposures to millions of potential mixtures of 86 aromatase inhibitors...
July 19, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28884392/socioeconomic-status-and-breast-cancer-treatment
#10
REVIEW
Marie S Dreyer, Ann B Nattinger, Emily L McGinley, Liliana E Pezzin
PURPOSE: Evidence suggests substantial disparities in breast cancer survival by socioeconomic status (SES). We examine the extent to which receipt of newer, less invasive, or more effective treatments-a plausible source of disparities in survival-varies by SES among elderly women with early-stage breast cancer. METHODS: Multivariate regression analyses applied to 11,368 women (age 66-90 years) identified from SEER-Medicare as having invasive breast cancer diagnosed in 2006-2009...
September 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28882552/prognostic-and-predictive-biomarkers-in-breast-cancer-past-present-and-future
#11
REVIEW
Andrea Nicolini, Paola Ferrari, Michael J Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients...
September 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28881223/efficacy-of-extended-adjuvant-therapy-with-aromatase-inhibitors-in-early-breast-cancer-among-common-clinicopathologically-defined-subgroups-a-systematic-review-and-meta-analysis
#12
REVIEW
Hadar Goldvaser, Ibrahim AlGorashi, Domen Ribnikar, Bostjan Seruga, Arnoud J Templeton, Alberto Ocana, Eitan Amir
BACKGROUND: Randomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically. METHODS: We identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016...
August 24, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28877935/targeting-aberrant-p70s6k-activation-for-estrogen-receptor-negative-breast-cancer-prevention
#13
Xiao Wang, Jun Yao, Jinyang Wang, Qingling Zhang, Samuel Warren Brady, Banu Arun, Victoria Seewaldt, Dihua Yu
The prevention of ER- breast cancer remains a major challenge in the cancer prevention field although anti-estrogen and aromatase inhibitors have shown adequate efficacy in preventing ER+ breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early stage lesions of patients. In the current study, we found that Akt and the downstream p70S6K signaling pathway was highly activated in ER- pre-malignant breast lesions and ER- breast cancer...
September 6, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28875723/ribociclib-for-post-menopausal-women-with-hr-her2-advanced-or-metastatic-breast-cancer
#14
Mark L Zangardi, Laura M Spring, Gayle C Blouin, Aditya Bardia
The introduction of CDK4/6 inhibitors, such as ribociclib, has changed the treatment landscape for post-menopausal women with HR+/HER2- advanced or metastatic breast cancer. As first-line treatment of HR+/HER2- MBC, the addition of a CDK4/6 inhibitor to an aromatase inhibitor improves progression-free survival compared to an aromatase inhibitor alone. Areas covered: In this drug profile, we review the current market for HR+/HER2- MBC, as well as the characteristics, mechanism, pharmacology, pharmacodynamics, pharmacokinetics, metabolism, clinical efficacy, toxicities, monitoring, and dosing modification of the CDK4/6 inhibitor ribociclib...
September 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28875319/kisspeptin-expression-features-in-the-arcuate-and-anteroventral-periventricular-nuclei-of-hypothalamus-of-letrozole-induced-polycystic-ovarian-syndrome-in-rats
#15
Elham Aliabadi, Mohammad Reza Namavar, Keywan Mortezaee, Heidar Toolee, Sara Keshtgar, Hossein Mirkhani, Mohammad Akbari, Tayebeh Rastegar, Somayeh Solhjoo
PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the reproductive system characterized by polycystic ovaries and androgen excess. Letrozole is a nonsteroidal aromatase inhibitor that is used in experimental research to induce PCOS. Kisspeptin is an essential protein in regulation of cyclicity. Kisspeptin receptor is expressed in the hypothalamus and pituitary glands, and kisspeptin containing neurons are affected from sex steroid hormones. We aimed to investigate the number of kisspeptin-positive cells in the arcuate (Arc) and anteroventral periventricular nuclei (AVPV) of hypothalamus in the letrozole-induced PCOS...
September 5, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28874599/survivorship-version-2-2017-nccn-clinical-practice-guidelines-in-oncology
#16
Crystal S Denlinger, Tara Sanft, K Scott Baker, Shrujal Baxi, Gregory Broderick, Wendy Demark-Wahnefried, Debra L Friedman, Mindy Goldman, Melissa Hudson, Nazanin Khakpour, Allison King, Divya Koura, Elizabeth Kvale, Robin M Lally, Terry S Langbaum, Michelle Melisko, Jose G Montoya, Kathi Mooney, Javid J Moslehi, Tracey O'Connor, Linda Overholser, Electra D Paskett, Jeffrey Peppercorn, M Alma Rodriguez, Kathryn J Ruddy, Paula Silverman, Sophia Smith, Karen L Syrjala, Amye Tevaarwerk, Susan G Urba, Mark T Wakabayashi, Phyllis Zee, Deborah A Freedman-Cass, Nicole R McMillian
Many cancer survivors experience menopausal symptoms, including female survivors taking aromatase inhibitors or with a history of oophorectomy or chemotherapy, and male survivors who received or are receiving androgen-ablative therapies. Sexual dysfunction is also common in cancer survivors. Sexual dysfunction and menopause-related symptoms can increase distress and have a significant negative impact on quality of life. This portion of the NCCN Guidelines for Survivorship provide recommendations for screening, evaluation, and treatment of sexual dysfunction and menopausal symptoms to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period...
September 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28874104/ovarian-stimulation-in-patients-with-cancer-impact-of-letrozole-and-brca-mutations-on-fertility-preservation-cycle-outcomes
#17
Volkan Turan, Giuliano Bedoschi, Volkan Emirdar, Fred Moy, Kutluk Oktay
BACKGROUND: Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28868654/impact-of-the-oatp1b1-c-521t-c-single-nucleotide-polymorphism-on-the-pharmacokinetics-of-exemestane-in-healthy-post-menopausal-female-volunteers
#18
B J Gregory, S M Chen, M A Murphy, D H Atchley, L K Kamdem
WHAT IS KNOWN AND OBJECTIVE: OATP1B1 mediates the transport of a diverse range of amphiphilic organic compounds that include bile acids, steroid conjugates and hormones. This retrospective pharmacogenetic study was conducted to assess the impact of the OATP1B1 c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthy volunteers. METHODS: Exemestane (25 mg) was administered orally to 14 healthy post-menopausal women...
October 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28868359/immune-mediator-pharmacogenomics-tcl1a-snps-and-estrogen-dependent-regulation-of-inflammation
#19
Ming-Fen Ho, Richard M Weinshilboum
This review describes the important functional implications of TCL1A single nucleotide polymorphisms (SNPs) discovered during pharmacogenomic studies of aromatase inhibitor-induced musculoskeletal adverse events that were subsequently shown to influence the expression of cytokines, chemokines, toll-like receptors (TLR), and NF-κB in a SNP and estrogen-dependent fashion. Functional genomic studies of these SNPs led to the discovery of novel mechanisms that may contribute to disease pathophysiology and which may also increase our understanding of pharmacogenomic aspects of regulation of the expression of inflammatory mediators...
August 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28862123/results-of-1-year-diet-and-exercise-interventions-for-er-pr%C3%A2-her2-breast-cancer-patients-correlated-with-treatment-type
#20
Diana V Artene, Cristian I Bordea, Alexandru Blidaru
PURPOSE: Many breast cancer patients gain weight during chemotherapy and antiestrogenic treatment increasing recurrence, oncologic specific and all-cause mortality risks. Patients and Methods: 165 ER+/PR±/HER2- breast cancer patients under antiestrogenic treatment were randomly assigned to follow an at-home diet based on food naturally high in proteins, calcium, probiotics and prebiotics (D), or this diet and 4' isometric exercises (D+Ex) for 1 year. We measured weight (W), body (BF) and visceral fat (VF) using a multi-frequency bioelectrical impedance scale on the 6th and 12th month and we correlated results with chemotherapy, surgery and antiestrogenic medication type...
July 2017: Chirurgia
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