scholarly journals Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis

2022 ◽  
Vol 24 ◽  
Author(s):  
Carmen Wing Han Chan ◽  
Caixia Li ◽  
Eleven Jinnan Xiao ◽  
Minjie Li ◽  
Patrick Gladson McLeywick Phiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Assessment Tool ◽  
Disease Free Survival ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Cytochrome P450 Enzymes ◽  
Free Survival ◽  
Meta Analyses

Abstract Tamoxifen is commonly prescribed for preventing recurrence in patients with breast cancer. However, the responses of the patients on tamoxifen treatment are variable. Cytochrome P450 genetic variants have been reported to have a significant impact on the clinical outcomes of tamoxifen treatment but no tangible conclusion can be made up till now. The present review attempts to provide a comprehensive review on the associative relationship between genetic polymorphisms in cytochrome P450 enzymes and survival in breast cancer patients on adjuvant tamoxifen therapy. The literature search was conducted using five databases, resulting in the inclusion of 58 studies in the review. An appraisal of the reporting quality of the included studies was conducted using the assessment tool from the Effective Public Health Practice Project (EPHPP). Meta-analyses were performed on CYP2D6 studies using Review Manager 5.3 software. For other studies, descriptive analyses were performed. The results of meta-analyses demonstrated that shorter overall survival, disease-free survival and relapse-free survival were found in the patients with decreased metabolisers when compared to normal metabolisers. The findings also showed that varying and conflicting results were reported by the included studies. The possible explanations for the variable results are discussed in this review.

Sequential Tamoxifen and Aminoglutethimide Versus Tamoxifen Alone in the Adjuvant Treatment of Postmenopausal Breast Cancer Patients: Results of an Italian Cooperative Study

2001 ◽  
Vol 19 (22) ◽  
pp. 4209-4215 ◽  
Author(s):  
F. Boccardo ◽  
A. Rubagotti ◽  
D. Amoroso ◽  
M. Mesiti ◽  
D. Romeo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Tamoxifen Group

PURPOSE: To determine whether switching patients from tamoxifen to antiaromatase treatment would prevent some of the relapses or deaths that we assume would occur if tamoxifen were continued. PATIENTS AND METHODS: Three hundred eighty postmenopausal breast cancer patients receiving adjuvant tamoxifen treatment for 3 years were randomized to either continue tamoxifen for 2 more years or to switch to low-dose aminoglutethimide (250 mg daily) for 2 years. RESULTS: At a median follow-up of 61 months (range, 5 to 94 months), 59 events occurred in the tamoxifen group, and 55 occurred in the aminoglutethimide group. More treatment failures at distant sites, such as viscera (P = .02), were observed in the tamoxifen group. Although no differences in disease-free survival between the two groups have emerged so far, a significant trend favors aminoglutethimide in overall survival (P = .005) and breast cancer–specific survival (P = .06). Even if more patients in the antiaromatase group complained of drug-related side effects and more of them discontinued treatment (P = .0001), the number of cardiovascular events and, in general, of life-threatening adverse events was higher in the tamoxifen arm. CONCLUSION: Switching patients from tamoxifen to aminoglutethimide treatment resulted in comparable event-free survival, but longer overall survival was achieved in patients who were switched to aminoglutethimide as compared with those who continued to receive tamoxifen. Should these preliminary results be confirmed by larger studies with a similar design, which are now testing the effectiveness of the new, more active, and tolerable aromatase inhibitors, sequencing tamoxifen with an aromatase inhibitor could become a preferable alternative to tamoxifen alone in early breast cancer patients.

Breast Cancer Treatment Outcome With Adjuvant Tamoxifen Relative to Patient CYP2D6 and CYP2C19 Genotypes

2007 ◽  
Vol 25 (33) ◽  
pp. 5187-5193 ◽  
Author(s):  
Werner Schroth ◽  
Lydia Antoniadou ◽  
Peter Fritz ◽  
Matthias Schwab ◽  
Thomas Muerdter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Treatment Outcome ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Tamoxifen Therapy ◽  
Tamoxifen Treatment ◽  
Adjuvant Tamoxifen ◽  
Breast Cancer Patients ◽  
Cytochrome P450 Enzymes

Purpose The clinical outcome of tamoxifen-treated breast cancer patients may be influenced by the activity of cytochrome P450 enzymes that catalyze the formation of antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. We investigated the predictive value of genetic variants of CYP2D6, CYP2C19, and three other cytochrome P450 enzymes for tamoxifen treatment outcome. Patients and Methods DNA from 206 patients receiving adjuvant tamoxifen monotherapy and from 280 patients not receiving tamoxifen therapy (71 months median follow-up) was isolated from archival material and was genotyped for 16 polymorphisms of CYP2D6, CYP2C19, CYP2B6, CYP2C9, and CYP3A5 by matrix-assisted, laser desorption/ionization, time-of-flight mass spectrometry, and by copy number quantification. Risk and survival estimates were calculated using logistic regression, Kaplan-Meier, and Cox regression analyses. Results Tamoxifen-treated patients carrying the CYP2D6 alleles *4, *5, *10, *41—all associated with impaired formation of antiestrogenic metabolites—had significantly more recurrences of breast cancer, shorter relapse-free periods (hazard ratio [HR], 2.24; 95% CI, 1.16 to 4.33; P = .02), and worse event-free survival rates (HR, 1.89; 95% CI, 1.10 to 3.25; P = .02) compared with carriers of functional alleles. Patients with the CYP2C19 high enzyme activity promoter variant *17 had a more favorable clinical outcome (HR, 0.45; 95% CI, 0.21 to 0.92; P = .03) than carriers of *1, *2, and *3 alleles. Conclusion Because genetically determined, impaired tamoxifen metabolism results in worse treatment outcomes, genotyping for CYP2D6 alleles *4, *5, *10, and *41 can identify patients who will have little benefit from adjuvant tamoxifen therapy. In addition to functional CYP2D6 alleles, the CYP2C19 *17 variant identifies patients likely to benefit from tamoxifen.

scholarly journals Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Tatyana A Seredina ◽  
Olga B Goreva ◽  
Valeria O Talaban ◽  
Alevtina Yu Grishanova ◽  
Vyacheslav V Lyakhovich
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Breast Cancer Patients ◽  
Chemotherapy Efficacy

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

scholarly journals Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 511 ◽  
Author(s):  
Viktor Hlavac ◽  
Maria Kovacova ◽  
Katerina Elsnerova ◽  
Veronika Brynychova ◽  
Renata Kozevnikovova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Cytotoxic Therapy ◽  
Free Survival ◽  
Testing Phase ◽  
Major Allele Frequency ◽  
Set Up ◽  
Disease Free

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASPTM technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized.

Sign in / Sign up

Export Citation Format

Share Document