Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment
| Autor: | Angela Seeringer, Uwe Langsenlehner, Alexander Kainz, Jürgen Brockmöller, Ariana Huber-Wechselberger, Sumit Parmar, Wilfried Renner, Peter Krippl, Elisabeth Haschke-Becher, Julia C. Stingl |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Oncology
medicine.medical_specialty Antineoplastic Agents Hormonal Genotype Estrogen receptor Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Outcome Assessment Health Care medicine Humans Progression-free survival skin and connective tissue diseases Survival analysis Aged Retrospective Studies 030304 developmental biology 0303 health sciences Polymorphism Genetic business.industry Retrospective cohort study General Medicine Middle Aged medicine.disease Survival Analysis 3. Good health Tamoxifen Cytochrome P-450 CYP2D6 Tumor progression Austria 030220 oncology & carcinogenesis Female business Pharmacogenetics medicine.drug |
| Zdroj: | Current Medical Research and Opinion. 26:2535-2542 |
| ISSN: | 1473-4877 0300-7995 |
| DOI: | 10.1185/03007995.2010.518304 |
| Popis: | 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 CYP2D6*4 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D6*4 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 CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D6*4 allele and missing data of comedication. |
| Databáze: | OpenAIRE |
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