522 results match your criteria: "Tamoxifen Metabolism and CYP2D6"
CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.
Cancer Epidemiol Biomarkers Prev
November 2024
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Article Synopsis
- The study assesses how systematic biases from loss of heterozygosity (LOH) and incomplete phenotyping affect the links between CYP2D6 genetic variants and breast cancer recurrence in women treated with tamoxifen.
- A systematic literature review and a quantitative bias analysis were conducted, leading to a meta-analysis which adjusted for these biases and found that individuals with poor CYP2D6 metabolism had a higher risk of breast cancer recurrence or mortality.
- The findings indicate that lower CYP2D6 activity correlates with increased breast cancer risks, highlighting the importance of addressing biases in research to better understand genetic impacts on health outcomes.
Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications.
Pharmacogenomics
November 2024
Department of Anatomy, Genetics & Biomedical Informatics, Faculty of Medicine, University of Colombo, Sri Lanka.
Article Synopsis
- Pharmacogenomics is gaining traction in South Asia, particularly in Sri Lanka, aiming to enhance drug therapies and minimize side effects for patients.
- A comprehensive review analyzed research in Sri Lanka, where studies were classified into categories like clinical correlational, descriptive, and novel assay development; 11 articles and 8 theses were reviewed.
- While progress has been made, additional clinical studies and a wider scope of genomic research are necessary, alongside efforts to address challenges like funding and public awareness, to successfully implement personalized medicine in the region.
Influence of endoxifen on mammographic density-results from the KARISMA trial.
J Natl Cancer Inst
November 2024
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Article Synopsis
- * In the KARISMA trial, 824 women were analyzed, finding that a decrease in MBD was linked to endoxifen levels of 2-3 ng/mL, particularly in those taking 5-10 mg doses of tamoxifen.
- * The research suggests a potential range of effective endoxifen levels for improving MBD in premenopausal women, but emphasizes the need for studies using established clinical outcomes for confirmation.
CYP2D6 activity in patients with metastatic breast cancer treated with single agent tamoxifen: results from ECOG-ACRIN E3108.
Breast Cancer Res Treat
October 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Article Synopsis
- - The study examined how genetic variations in the CYP2D6 gene and resulting endoxifen levels affect breast cancer outcomes in patients taking tamoxifen.
- - Conducted with 113 patients with advanced hormone receptor-positive breast cancer, it compared those with poor CYP2D6 metabolism to those with normal or intermediate metabolism regarding progression-free survival (PFS).
- - Results showed no significant relationship between CYP2D6 status, endoxifen concentrations, and PFS, possibly due to the small sample size and issues with sample collection in the trial.
Solanidine Metabolites as Diet-Derived Biomarkers of CYP2D6-Mediated Tamoxifen Metabolism in Breast Cancer Patients.
Clin Pharmacol Ther
November 2024
Department of Medicine, Western University, London, Ontario, Canada.
Article Synopsis
- Tamoxifen is a key treatment for hormone receptor-positive breast cancer, and its effectiveness depends on its conversion to the active form, endoxifen, by the enzyme CYP2D6.
- A study of 1,032 breast cancer patients found that metabolites of solanidine, a compound in potatoes, can indicate CYP2D6 activity and thus influence tamoxifen metabolism.
- Ratios of solanidine metabolites were linked to endoxifen levels, suggesting these metabolites may serve as biomarkers for assessing CYP2D6 activity and the impact of other medications before starting or switching breast cancer therapies.
Endoxifen Concentration is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.
Cancer Res Treat
June 2024
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Article Synopsis
- The study investigated how different levels of endoxifen, a metabolite of tamoxifen affected by cytochrome P450 enzymes, impact the recurrence-free survival (RFS) of breast cancer patients treated with tamoxifen.
- Involving 478 patients, researchers measured tamoxifen and its metabolites and found that an endoxifen level of 21.00 ng/mL is an optimal cutoff for predicting patient outcomes.
- Results showed that patients with higher endoxifen levels (> 21.00 ng/mL) had a significantly better 10-year recurrence-free survival rate compared to those with lower levels, suggesting that monitoring endoxifen could improve treatment strategies.
Frequency of pharmacogenomic variants affecting efficacy and safety of anti-cancer drugs in a south Asian population from Sri Lanka.
BMC Med Genomics
May 2024
Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
Article Synopsis
- Anti-cancer drug therapy is crucial for treating cancer but can vary in effectiveness and safety among individuals due to genetic differences, a factor that is not often addressed in Sri Lanka’s treatment guidelines.
- This study investigates pharmacogenomic variants in Sri Lankans by analyzing data from 541 individuals to identify how these genetic variations impact responses to specific anti-cancer drugs.
- Results show that certain genetic variants have notable frequencies in the Sri Lankan population, potentially guiding personalized therapy to enhance treatment outcomes.
Distribution of and gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China.
Open Life Sci
April 2024
Department of Breast Cancer Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, No. 789, Suzhou Road, Urumqi, Xinjiang, 830011, China.
Article Synopsis
- The study aimed to analyze the frequency of cytochrome P450 enzymes and tamoxifen metabolism in premenopausal breast cancer patients from Han and Uygur ethnic groups in Xinjiang to help with better drug usage.
- A total of 246 patients were examined, revealing significant differences in specific genotypes between the Han and Uygur groups, but no significant differences in their tamoxifen metabolization phenotypes.
- The findings suggest that while there are some genotypic variations, they do not affect the overall tamoxifen metabolism, indicating that dosing should still be individualized based on the patient's genotype.
A Genome-Wide Association Study of Endoxifen Serum Concentrations and Adjuvant Tamoxifen Efficacy in Early-Stage Breast Cancer Patients.
Clin Pharmacol Ther
July 2024
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Article Synopsis
- - Tamoxifen is commonly used in breast cancer treatment, but how effective it is can vary significantly among patients, primarily due to differing levels of its active metabolite, endoxifen.
- - A genome-wide association study (GWAS) involving 608 women aimed to find genetic factors that influence endoxifen levels and patient survival outcomes, revealing multiple significant genetic variants.
- - The study found that certain genetic variants on chromosome 22, including those linked to the CYP2D6 gene, are strongly associated with both endoxifen concentration and relapse-free survival in breast cancer patients on tamoxifen.
Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort.
Clin Pharmacol Ther
September 2024
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
Tamoxifen 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 are considered infeasible.
View Article and Find Full Text PDFPharmacogenetics of tamoxifen in breast cancer patients of African descent: Lack of data.
Clin Transl Sci
March 2024
Platform for Pharmacogenomics Research and Translation (PREMED), South African Medical Research Council, Cape Town, South Africa.
Article Synopsis
- * The drug's effectiveness is influenced by various genetic factors and its metabolism by specific enzymes, which differ among populations worldwide.
- * There is a notable lack of pharmacogenetic research on tamoxifen in African populations, emphasizing the need for targeted studies to enhance treatment outcomes and reduce side effects for African breast cancer patients.
The landscape of very important pharmacogenes variants and potential clinical relevance in the Chinese Jingpo population: a comparative study with worldwide populations.
Cancer Chemother Pharmacol
May 2024
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, #229 North TaiBai Road, Xi'an, 710069, Shaanxi, China.
Article Synopsis
- Pharmacogenomics studies how genetic differences influence drug metabolism and reactions, aiming to understand these variations in the Jingpo population.
- The research used the Agena MassARRAY Assay to analyze 57 genetic variants in 159 Jingpo individuals, comparing their data to 26 other populations.
- Key findings included identifying six significant genetic loci associated with drug metabolism and toxicity, which could impact treatment efficacy and safety for Jingpo individuals.
Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers.
Drug Metab Dispos
January 2024
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.)
Article Synopsis
- * A genome-wide association study (GWAS) was conducted to find new genetic variants linked to CYP2D6 protein expression and activity, resulting in the identification of 44 significant single nucleotide polymorphisms (SNPs).
- * Five of these SNPs, including notable variants, were found to significantly impact CYP2D6 protein levels and enzyme activity, suggesting their importance in drug metabolism variability among individuals.
The interplay between tamoxifen and endoxifen plasma concentrations and coagulation parameters in patients with primary breast cancer.
Biomed Pharmacother
January 2024
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Article Synopsis
- Tamoxifen is an effective breast cancer treatment but raises the risk of blood clots, with unknown effects of its plasma levels on coagulation.
- A study measured tamoxifen and its active form, endoxifen, in 141 patients after 3 and 6 months of treatment, analyzing their correlation with anticoagulant proteins and thrombin generation.
- The results showed that higher levels of tamoxifen and endoxifen were not linked to increased blood coagulation risk, indicating that increasing the dose may not further enhance clot risk.
Clinical Guidance for Dosing and Monitoring Oral Antihormonal Drugs in Patients with Breast Cancer After Roux-en-Y Gastric Bypass.
Ther Drug Monit
June 2024
Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein/Utrecht, the Netherlands.
Article Synopsis
- * A study of 9 patients post-RYGB showed that most did not achieve therapeutic levels of the antihormonal drug tamoxifen at the standard dosage, leading to a recommendation for a higher starting dose in some cases.
- * Patients with altered CYP2D6 metabolism may need to switch to different treatments, and while no dose adjustments were necessary for other drugs like anastrozole and letrozole, ongoing monitoring for effectiveness is still advised.
Evaluation of the effect of CYP2D6*3, *4,*10, and *17 polymorphisms on the pharmacokinetic of tamoxifen and its metabolites in patients with hormone-positive breast cancer.
J Pharm Biomed Anal
January 2024
Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Article Synopsis
- - The study examines how the CYP2D6 gene polymorphism influences breast cancer patients' responses to tamoxifen (TAM) treatment, noting interindividual variability in therapeutic outcomes.
- - Researchers analyzed blood samples to measure TAM and its metabolites using HPLC-FLU and identified specific CYP2D6 genetic variants in a group of Iranian women with breast cancer.
- - Results indicated that while poor or intermediate metabolizers had lower plasma concentrations of tamoxifen metabolites compared to extensive metabolizers, the differences were not statistically significant, highlighting the complexity of individual responses to treatment.
genotyping and the clinical impact on outcomes in breast cancer tamoxifen-treated patients.
Per Med
November 2023
Molecular Genetic Unit, School of Chemistry, Universidad de la República, Montevideo, 11800, Uruguay.
Article Synopsis
- The study analyzed allele frequencies of a specific gene in 199 breast cancer patients from Uruguay undergoing tamoxifen treatment to see how it affected their clinical outcomes.
- Genotyping was done using real-time polymerase chain reaction, revealing metabolization profiles: 65% normal, 30% intermediate, and 5% poor metabolizers.
- Findings indicated no significant impact of gene polymorphisms on clinical outcomes, as the normal metabolizers had similar results to the combined intermediate and poor metabolizer groups.
Design, synthesis, and in-silico study of novel triarylethylene analogs with dual anti-estrogenic and serotonergic activity.
Drug Dev Res
February 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
Article Synopsis
- * Researchers are exploring selective estrogen receptor modulators (SERMs) with serotonergic activity that could enhance the effects of existing treatments while addressing menopausal symptoms and improving cognitive and bone health.
- * Triarylethylene analogs were identified as promising candidates, with compounds 2e and 4e showing significantly greater potency against breast cancer cell lines (MCF-7 and MDA-MB-231) compared to the standard treatment tamoxifen (TAM), alongside in-silico modeling indicating potential for optimization.
Pharmacogenetics and pharmacokinetics of tamoxifen in a Zimbabwean breast cancer cohort.
Br J Clin Pharmacol
October 2023
Department of Genomic Medicine, African Institute of Biomedical Science and Technology (AiBST), Beatrice, Zimbabwe.
Article Synopsis
- * A study involving 40 breast cancer patients in Zimbabwe found that many had genetic variants (polymorphisms) in CYP2D6 that affect drug metabolism, leading to lower endoxifen levels.
- * Results showed that 55% of participants had endoxifen concentrations below the therapeutic threshold, highlighting a significant relationship between CYP2D6 genetic variations and endoxifen levels (with specific statistical significance).
The pharmacogenomic landscape of an Indigenous Australian population.
Front Pharmacol
May 2023
Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia.
Article Synopsis
- Population genomic studies on Indigenous peoples are scarce, comprising less than 0.5% of genetic database participants, which hinders access to personalized medicine for these communities.
- A pharmacogenomic study on nearly 500 individuals from the Tiwi population used whole genome sequencing and found that all participants carried at least one actionable genotype, with 77% having three or more clinically significant variants.
- Significant findings included a notably high frequency of impaired metabolism for various important pharmacogenes in the Tiwi population, which may affect the treatment and safety of several common medications, highlighting the need for tailored healthcare approaches.
Profiling of pharmacogenomic variants in and in indigenous Arab breast cancer patients.
Pharmacogenomics
May 2023
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Article Synopsis
- * Exome sequencing of 220 Arab female breast cancer patients revealed that 5.9% had clinically actionable results, while 25.5% carried unknown-impact alleles related to drug metabolism.
- * Four novel missense variants were identified, including one highly likely to be pathogenic, indicating the necessity for further research to enhance understanding of pharmacogenomics in this population.
Effects of Genetic Polymorphisms of Drug Metabolizing Enzymes and co-Medications on Tamoxifen Metabolism in Black South African Women with Breast Cancer.
Clin Pharmacol Ther
July 2023
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Article Synopsis
- Clinical outcomes of tamoxifen (TAM) treatment show high variability among individuals, influenced by genetic differences and other medications.
- A study involving 229 South African Black women with breast cancer found that certain genetic variants (CYP2D6*17 and CYP2D6*29) significantly impact the metabolism of TAM and its active metabolites.
- While antiretroviral therapy affected certain metabolite levels of TAM, the overall risk of significant drug interactions was considered low for patients undergoing TAM treatment.
Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis.
Breast
June 2023
Biosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain; Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain.
Article Synopsis
- - The study investigates the impact of an increased tamoxifen dosage on breast cancer survival in patients who metabolize the drug poorly due to variations in the CYP2D6 enzyme.
- - A total of 220 breast cancer patients participated, with treatment adjustments made for poor metabolizers; however, the study found no significant differences in disease-free and overall survival based on CYP2D6 variations.
- - Key factors affecting survival included age, histological grade, nodal status, and chemotherapy, but increasing tamoxifen dosage did not improve outcomes for patients with different CYP2D6 phenotypes.
Short-term changes in ultrasound tomography measures of breast density and treatment-associated endocrine symptoms after tamoxifen therapy.
NPJ Breast Cancer
March 2023
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Article Synopsis
- A study examined the relationship between treatment-associated endocrine symptoms and breast density changes in women taking tamoxifen for breast cancer over 12 months.
- Results indicated that women experiencing endocrine symptoms showed significant declines in breast density, while those without symptoms did not.
- Further research is needed to determine if these changes in breast density can predict better clinical outcomes, suggesting that endocrine symptoms might be a valuable indicator of tamoxifen effectiveness.
Adherence to endocrine therapy in early breast cancer in relation to Cytochrome P450 2D6 genotype: a comparison between pharmacy dispensation data and medical records.
Breast Cancer Res Treat
April 2023
Department of Laboratory Medicine, Clinical Pharmacology, Karolinska Institutet and Medical Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
Article Synopsis
- - The study aimed to evaluate the consistency between pharmacy dispensation data and medical records concerning patients' adherence to adjuvant endocrine treatment (AET), particularly tamoxifen, over 4.5 years.
- - Results showed that 86% of the 1235 patients had consistent adherence rates between 80-125%, with poorer consistency seen in premenopausal high-risk individuals and those with low CYP2D6 activity.
- - While overall adherence rates were satisfactory, CYP2D6 Poor Metabolizers (PMs) exhibited significantly lower tamoxifen adherence (54%) compared to patients with higher CYP2D6 activity (83%).