Institute of Pharmacology of Natural Compounds and Clinical Pharmacology, University Ulm, Germany.
Curr Med Res Opin. 2010 Nov;26(11):2535-42. doi: 10.1185/03007995.2010.518304. Epub 2010 Sep 17.
The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy.
A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction. All women with estrogen receptor positive tumors and tamoxifen therapy longer than 6 months were genotyped for CYP2D6*4 using TaqMan technology. Time to tumor progression, defined as local, regional, distant recurrence or contralateral breast cancer and progression free survival, was analyzed.
No significant difference in time to tumor progression or progression free survival between the CYP2D64 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D64 poor metabolizers had a tendency towards a shorter mean time to progression. In this group the mean time to tumor progression and the progression free survival were 1.0 years in the CYP2D6*4/*4 group, 6.3 years in the *1/*4 group and 4.97 years in the *1/*1 group (Wilcoxon p = 0.104).
While earlier data on CYP2D6 and tamoxifen excluded women with prior chemotherapy, the present analysis suggests that CYP2D64 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D64 allele and missing data of comedication.
细胞色素 P450 2D6（CYP2D6）多态性被报道对雌激素受体阳性乳腺癌患者接受他莫昔芬治疗的结果有重大影响。本研究的目的是在包括先前接受过化疗的女性在内的单个临床试验队列中探索 CYP2D6*4 多态性对他莫昔芬治疗结果的影响。
对奥地利 TIGER 研究的 493 例接受辅助他莫昔芬治疗的患者进行了这项遗传药理学相互作用的研究。所有雌激素受体阳性肿瘤且他莫昔芬治疗时间超过 6 个月的女性均采用 TaqMan 技术进行 CYP2D6*4 基因分型。分析肿瘤进展时间（定义为局部、区域、远处复发或对侧乳腺癌以及无进展生存期）。
在整个研究队列中，CYP2D64 基因型组之间在肿瘤进展时间或无进展生存期方面没有显著差异。在接受化疗的患者亚组中，CYP2D64 弱代谢者的平均进展时间有缩短的趋势。在该组中，CYP2D6*4/*4 组的平均肿瘤进展时间和无进展生存率为 1.0 年，*1/*4 组为 6.3 年，*1/*1 组为 4.97 年（Wilcoxon p = 0.104）。
尽管早期关于 CYP2D6 和他莫昔芬的数据排除了有既往化疗史的女性，但本分析表明，CYP2D64 基因型在这组高危患者中可能特别重要。主要限制因素是 CYP2D64 等位基因的限制和伴随用药数据的缺失。
