A Genome-Wide Association Study of Endoxifen Serum Concentrations and Adjuvant Tamoxifen Efficacy in Early-Stage Breast Cancer Patients
Clin Pharmacol Ther. 2024 Mar 19. doi: 10.1002/cpt.3255. Online ahead of print.ABSTRACTTamoxifen is part of the standard of care of endocrine therapy for adjuvant treatment of breast cancer. However, survival outcomes with tamoxifen are highly variable. The concentration of endoxifen, the 30-100 times more potent metabolite of tamoxifen and bioactivated by the CYP2D6 enzyme, has been described as the most relevant metabolite of tamoxifen metabolism. A genome-wide association study (GWAS) was performed with the objective to identify genetic polymorphisms associated with endoxifen serum concentration levels and clinical outc...
Source: Clinical Pharmacology and Therapeutics - March 19, 2024 Category: Drugs & Pharmacology Authors: Anabel Beatriz Sanchez-Spitman Stefan B öhringer Vincent Olaf Dezentj é Hans Gelderblom Jesse Joachim Swen Henk-Jan Guchelaar Source Type: research
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Breast Cancer - March 18, 2024 Category: Cancer & Oncology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Genitourinary Cancer - March 18, 2024 Category: Cancer & Oncology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Pharmacology and Therapeutics - March 18, 2024 Category: Drugs & Pharmacology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Breast Cancer - March 18, 2024 Category: Cancer & Oncology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Genitourinary Cancer - March 18, 2024 Category: Cancer & Oncology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research
Towards clinical adherence monitoring of oral endocrine breast cancer therapies by LC-HRMS-method development, validation, comparison of four sample matrices, and proof of concept
Anal Bioanal Chem. 2024 Mar 15. doi: 10.1007/s00216-024-05244-6. Online ahead of print.ABSTRACTOral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetr...
Source: Analytical and Bioanalytical Chemistry - March 15, 2024 Category: Chemistry Authors: Cathy M Jacobs Julia C Radosa Lea Wagmann Julia S M Zimmermann Askin C Kaya Aylin Ayg ün Tatjana Edel Lisa Stotz Mohamed Ismaeil Erich-Franz Solomayer Markus R Meyer Source Type: research
GSE261462 Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer
Contributors : Jiahui Zhang ; Nanyan Miao ; Liyan LaoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBasal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis. POU4F1 is necessary for the tumor growth and malignant...
Source: GEO: Gene Expression Omnibus - March 14, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
GSE227384 Possible involvement of transient receptor potential channels in adenomyosis
Contributors : Zhixing Jin ; Yaoming Peng ; He Zhang ; Xiaoping He ; Yi Zhang ; Xinwei Zou ; Xin Pan ; Min Li ; Qianqian YangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTo investigate the role and mechanism of the TRPM3 antagonist, primidone in tamoxifen-induced adenomyosis mouse.The neonatal female mice were randomly divided into three groups: control group, adenomyosis group and primidone treatment group. We then performed gene expression profiling analysis using data obtained from RNA-seq of uterus from different groups (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - March 14, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?
AbstractTamoxifen, a cornerstone in the adjuvant treatment of estrogen receptor-positive breast cancer, significantly reduces breast cancer recurrence and breast cancer mortality; however, its standard adjuvant dose of 20 mg daily presents challenges due to a broad spectrum of adverse effects, contributing to high discontinuation rates. Dose reductions of tamoxifen might be an option to reduce treatment-related toxicity, but large randomized controlled trials investigating the tolerability and, more importantly, efficacy of low-dose tamoxifen in the adjuvant setting are lacking. We conducted an extensive literature search ...
Source: Drugs - March 14, 2024 Category: Drugs & Pharmacology Source Type: research
Pharmacogenetics of tamoxifen in breast cancer patients of African descent: Lack of data
Clin Transl Sci. 2024 Mar;17(3):e13761. doi: 10.1111/cts.13761.ABSTRACTTamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor-positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug-metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenet...
Source: Clinical Breast Cancer - March 13, 2024 Category: Cancer & Oncology Authors: Bianca Kruger Delva Shamley Nyarai Desiree Soko Collet Dandara Source Type: research
Pharmacogenetics of tamoxifen in breast cancer patients of African descent: Lack of data
Clin Transl Sci. 2024 Mar;17(3):e13761. doi: 10.1111/cts.13761.ABSTRACTTamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor-positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug-metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenet...
Source: Clinical Genitourinary Cancer - March 13, 2024 Category: Cancer & Oncology Authors: Bianca Kruger Delva Shamley Nyarai Desiree Soko Collet Dandara Source Type: research
Erdheim ‑Chester disease of multisystem involvement with delayed diagnosis: A case report and literature review
Exp Ther Med. 2024 Feb 22;27(4):159. doi: 10.3892/etm.2024.12447. eCollection 2024 Apr.ABSTRACTErdheim-Chester disease (ECD) is a rare tumor of histiocytic origin, characterized by foamy or lipid-laden histiocytes mixed or surrounded by fibrosis that infiltrate multiple organs. Misdiagnosis is common due to the diversity of clinical presentations. The present study reported a case of ECD with the involvements of bone, cardiac, aorta and retroperitoneum. The patient had no obvious clinical symptoms and no noteworthy foamy histiocytes or Touton giant cells were found on pathological examination, delaying the diagnosis. The p...
Source: Experimental and Therapeutic Medicine - March 13, 2024 Category: General Medicine Authors: Xiaotong Shi Guangzhi Sun Tongguan Li Mengjiao Xu Yixuan Liu Zhankui Wang Yanfeng Hou Source Type: research
Pharmacogenetics of tamoxifen in breast cancer patients of African descent: Lack of data
Clin Transl Sci. 2024 Mar;17(3):e13761. doi: 10.1111/cts.13761.ABSTRACTTamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor-positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug-metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenet...
Source: Clinical Breast Cancer - March 13, 2024 Category: Cancer & Oncology Authors: Bianca Kruger Delva Shamley Nyarai Desiree Soko Collet Dandara Source Type: research
