Research
Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment
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* Corresponding author: Wendy Lorizio wlorizio@medicine.ucsf.edu
1 Division of General Internal Medicine, Department of Medicine, University of California San Francisco, 1545 Divisadero Street, Suite 322, San Francisco, CA 94143-0320, USA
2 Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California San Francisco, San Francisco General Hospital Medical Center, 1001 Potrero Avenue, Building 30, 2nd Floor, Room 3216, San Francisco, CA 94143-1220, USA
3 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero Street, San Francisco, CA 94143, USA
4 Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, 1600 Divisadero Street, Room B-608, San Francisco, CA 94143-1710, USA
5 Department of Epidemiology and Biostatistics, University of California San Francisco, 185 Berry Street, Lobby 5, Suite 5700, San Francisco, CA 94107, USA
6 Institute for Human Genetics, University of California San Francisco, 513 Parnassus Avenue, Suite S965, San Francisco, CA 94143-0794, USA
7 Department of Biopharmaceutical Sciences, University of California San Francisco, 1700 Fourth Street, Byers Hall, Suite BH-216, San Francisco, CA 94143-0775, USA
8 Department of Medicine, School of Medicine, Dean's Office, University of California San Francisco, 513 Parnassus Avenue, Medical Science Building 224, San Francisco, CA 94143-0410, USA
9 Department of Laboratory Medicine, University of California San Francisco, 1001 Potrero Avenue, SFGH 5 2M27, San Francisco, CA 94143, USA
10 Roche Molecular Systems, Inc., 4300 Hacienda Drive, Pleasanton, CA 94588, USA
Genome Medicine 2011, 3:64 doi:10.1186/gm280
Published: 4 October 2011Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.