The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review

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dc.contributor.author Fleeman, N. spa
dc.contributor.author Martín Saborido, Carlos spa
dc.contributor.author Payne, K. spa
dc.contributor.author Boland, A. spa
dc.contributor.author Dickson, R. spa
dc.contributor.author Dundar, Y. spa
dc.contributor.author Fernández Santander, Ana spa
dc.contributor.author Howell, S. J. spa
dc.contributor.author Newman, W. G. spa
dc.contributor.author Oyee, J. spa
dc.contributor.author Walley, T. spa
dc.date.accessioned 2013-11-27T17:25:56Z
dc.date.available 2013-11-27T17:25:56Z
dc.date.issued 2011 spa
dc.identifier.citation Fleeman, N., Martín-Saborido, C., Payne, K., Boland, A., Dickson, R., Dundar, Y., ..., & Walley, T. (2011). The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review. Health Technology Assessment, 15(33), 1-126. spa
dc.identifier.issn 13665278 spa
dc.identifier.uri http://hdl.handle.net/11268/303
dc.description.abstract Background: Objectives: Data Sources: Review Methods: Results: Conclusion: Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the standard of care for many women with oestrogen receptor positive breast cancer. However, wide variability in the response of individuals to drugs at the same doses may occur, which may be a result of interindividual genetic differences (pharmacogenetics). TAM is known to be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and CYP2B6. N-desmethyl TAM is further metabolised to endoxifen by CYP2D6. Endoxifen, which is also formed via the action of CYP2D6, is 30- to 100-fold more potent than TAM in suppressing oestrogen-dependent cell proliferation, and is considered an entity responsible for significant pharmacological effects of TAM. Thus, an association between the cytochrome P450 2D6 (CYP2D6) genotype and phenotype (expected drug effects) is believed to exist and it has been postulated that CYP2D6 testing may play a role in optimising an individual's adjuvant hormonal treatment.To determine whether or not testing for cytochrome P450 2D6 (CYP2D6) polymorphisms in women with early hormone receptor positive breast cancer leads to improvement in outcomes, is useful for health decision-making and is a cost-effective use of health-care resources.Relevant electronic databases and websites including MEDLINE, EMBASE and HuGENet [Centers for Disease Control and Prevention (Office of Public Health Genomics), Human Genome Epidemiology Network] were searched until July 2009. Further studies that became known to the authors via relevant conferences or e-mail alerts from an automatically updated search of the Scopus database were also included as the review progressed, up to March 2010.A systematic review of the clinical effectiveness and cost-effectiveness of CYP2D6 testing was undertaken. As it was not possible to conduct meta-analyses, data were extracted into structured tables and narratively discussed. An exploratory analysis of sensitivity and specificity was undertaken. A review of economic evaluations and models of CYP2D6 testing for patients treated with TAM was also carried out.A total of 25 cohorts were identified which examined clinical efficacy (overall survival and relapse/recurrence), adverse events and endoxifen plasma concentrations by genotype/phenotype. Significantly, six cohorts suggest extensive metabolisers (Ems) appear to have better outcomes than either poor metabolisers (PMs) or PMs + intermediate metabolisers in terms of relapse/recurrence; however, three cohorts report apparently poorer outcomes for EMs (albeit not statistically significant). There was heterogeneity across the studies in terms of the patient population, alleles tested and outcomes used and defined. One decision model proposing a strategy for CYP2D6 testing for TAM was identified, but this was not suitable for developing a model to examine the cost-effectiveness of CYP2D6 testing. It was not possible to produce a de novo model because of a lack of data to populate it.This is a relatively new area of research that is evolving rapidly and, although international consortia are collaborating, the data are limited and conflicting. Therefore, it is not possible to recommend pharmacogenetic testing in this patient population. Future research needs to focus on which alleles (including, or in addition to, those related to CYP2D6) reflect patient response, the link between endoxifen levels and clinical outcomes, and the appropriate pathways for implementation of such pharmacogenetic testing in patient care pathways. spa
dc.language.iso eng spa
dc.subject.other Genotype* spa
dc.subject.other Antineoplastic Agents, Hormonal/*Therapeutic Use spa
dc.subject.other Breast Neoplasms/*Genetics spa
dc.subject.other Cytochrome P-450 Cyp2d6/*Genetics spa
dc.subject.other Tamoxifen/*Therapeutic Use spa
dc.subject.other Antineoplastic Agents, Hormonal/Metabolism spa
dc.subject.other Antineoplastic Agents, Hormonal/Pharmacology spa
dc.subject.other Breast Neoplasms/Drug Therapy spa
dc.subject.other Breast Neoplasms/Economics spa
dc.subject.other Cost-Benefit Analysis spa
dc.subject.other Female spa
dc.subject.other Great Britain spa
dc.subject.other Humans spa
dc.subject.other Markov Chains spa
dc.subject.other Mortality spa
dc.subject.other Neoplasm Recurrence, Local spa
dc.subject.other Pharmacogenetics spa
dc.subject.other Phenotype spa
dc.subject.other Prognosis spa
dc.subject.other Sensitivity and Specificity spa
dc.subject.other Tamoxifen/Metabolism spa
dc.subject.other Tamoxifen/Pharmacology spa
dc.subject.other Treatment Outcome spa
dc.title The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review spa
dc.type article spa
dc.description.impact 4.255 JCR (2011) Q1, 4/76 Health care sciences & services spa
dc.identifier.doi 10.3310/hta15330 spa
dc.rights.accessRights openAccess en
dc.subject.unesco Cáncer spa
dc.subject.unesco Tratamiento médico spa
dc.subject.unesco Salud de la mujer spa
dc.peerreviewed Si spa

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