Clinical Implications of CYP2D6 Genotyping in Tamoxifen Treatment for Breast Cancer

被引:65
作者
Dezentje, Vincent O. [1 ,2 ]
Guchelaar, Henk-Jan [2 ]
Nortier, Johan W. R. [1 ]
van de Velde, Cornelis J. H. [3 ]
Gelderblom, Hans [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Clin Oncol, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2300 RC Leiden, Netherlands
基金
澳大利亚研究理事会;
关键词
CYTOCHROME-P450; 2D6; METABOLIZING ENZYMES; ENDOCRINE THERAPY; ADJUVANT BREAST; GENE; POLYMORPHISM; PHARMACOGENETICS; FREQUENCIES; POPULATION; SURVIVAL;
D O I
10.1158/1078-0432.CCR-08-2006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In October 2006 the Food and Drug Administration recommended an update in the tamoxifen label to reflect the increased risk of recurrence in breast cancer patients who are cytochrome P450 2D6 (CYP2D6) poor metabolizers. This recommendation was based on only a few studies at that time, More clinical studies addressing the relation between the CYP2D6 genotype and tamoxifen efficacy have been published since, mostly describing Caucasian populations in the adjuvant treatment setting. An updated analysis of the literature is presented. Furthermore, the possibility to implement CYP2D6 genotyping in clinical practice is evaluated by analyzing the results of six studies on mainly Caucasian patients using adjuvant tamoxifen. Three studies were consistent with the FDA advice, but the three other studies showed contradictory results. Although some of the published criticism on the negative studies is justified, this does not imply that these results should be discarded. The reviewed literature is put in perspective acknowledging the limiting effect of Mendelian randomization on confounding and the limitations of the various study designs. The current accumulation of data showing worse clinical outcome in patients with decreased CYP2D6 metabolism in other types of populations still indicates that the CYP2D6 genotype may well become a clinically relevant predictive marker. The CYP2D6 genotype might be one of the first predictors of therapeutic response in cancer care based on germline DNA creating the possibility to analyze blood instead of tumor.
引用
收藏
页码:15 / 21
页数:7
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