Division of General Internal Medicine, Department of Medicine, University of California San Francisco, 1545 Divisadero Street, Suite 322, San Francisco, CA 94143-0320, USA.
Genome Med. 2011 Oct 4;3(10):64. doi: 10.1186/gm280.
Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study.
Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication.
A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P < 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6.
CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact.
药物遗传学检测有望让医生根据患者的基因型为其量身定制治疗方案。然而，关于药物遗传学检测结果对患者和临床医生治疗选择的影响的数据却很少。他莫昔芬使用者的 CYP2D6 检测为临床中使用药物遗传学检测提供了一个潜在的案例。我们评估了 CYP2D6 检测在临床实践中的效果，以确定基因型结果是否会影响激素治疗的选择，这是一项前瞻性队列研究。
计划或正在服用他莫昔芬的女性被认为符合条件。参与者参加了一个信息会议，会上回顾了 CYP2D6 基因型对乳腺癌复发的研究结果。使用 AmpliChip CYP450 检测对参与者进行 CYP2D6 基因分型。女性被分为弱代谢者、中间代谢者、广泛代谢者或超快代谢者。结果提供给临床医生，但没有具体的治疗建议。在检测后 3 至 6 个月进行了结构电话随访，以评估药物的变化。
共有 245 名女性接受了检测，其中 235 名完成了随访调查。在被归类为弱代谢者的 13 名女性中，有 6 名（46%）报告改变了治疗方法，而在被归类为中间代谢者、广泛代谢者或超快代谢者的 218 名女性中，有 11 名（5%）报告改变了治疗方法（P < 0.001）。中间代谢者和广泛代谢者之间的治疗选择没有差异。在调整年龄、种族/民族、教育程度、研究入组方式、对 CYP2D6 检测的先前了解、患者 CYP2D6 基因型等因素的多变量模型中，治疗方法改变的唯一显著因素是患者的 CYP2D6 基因型（比值比 22.8；95%置信区间 5.2 至 98.8）。基因检测并未影响与 CYP2D6 相互作用的共用药的使用。
即使缺乏替代药物改善结局的确切数据，CYP2D6 基因型检测也会导致弱代谢者的治疗方法发生变化。即使缺乏药物遗传学检测对临床影响的确切数据，它也会影响治疗选择。
