Research article
Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer
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* Corresponding author: Elisabeth Haschke-Becher elisabeth.haschke@elisabethinen.or.at
1 Institute of Pharmacology of Natural Products and Clinical Pharmacology, University Ulm, Helmholtzstrasse 20, Ulm, 89081, Germany
2 Institute of Medical and Laboratory Diagnostics, Elisabethinen Hospital Linz, Fadingerstrasse 1, Linz, 4020, Austria
3 Department of Nephrology and Dialysis, Medical University Vienna, Währingergürtel 18-20, Vienna, 1090, Austria
4 Clinical Institute of Medical and Laboratory Diagnostics, Medical University Graz, Auenbruggerplatz 15, Graz, 8036, Austria
5 Department of Internal Medicine, Hospital of Fürstenfeld, Krankenhausgasse 1, Fürstenfeld, 8280, Austria
6 Department of Clinical Pharmacology, University Göttingen, Robert-Koch-Strasse 40, Göttingen, 37075, Germany
7 Christian Doppler Clinic, Private Paracelsus Medical University Salzburg, Ignaz Harrerstrasse 79, Salzburg, 5020, Austria
Breast Cancer Research 2011, 13:R57 doi:10.1186/bcr2894
Published: 9 June 2011Abstract
Introduction
Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7His268Tyr polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.
Methods
This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the Austrian Tumor of breast tissue: Incidence, Genetics, and Environmental Risk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all women UGT2B7His268Tyr was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis.
Results
Among the 205 epirubicin-treated patients, carriers of two UGT2B7268Tyr alleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least one UGT2B7268His allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7His268Tyr polymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04); P = 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin.
Conclusions
Breast cancer patients carrying the UGT2B7268Tyr/Tyr genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.