Abstract
BackgroundPharmacogenetic 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.MethodsWomen 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.ResultsA 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.ConclusionsCYP2D6 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.
Highlights
Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype
Patients were recruited by physician referral or after receiving a contact letter sent to all patients from the University of California San Francisco (UCSF) Breast Oncology Clinic who met eligibility criteria
Most of the women enrolled in the study (97%) had either invasive breast cancer or ductal carcinoma in situ (DCIS) with the majority (70%) reporting invasive breast cancer
Summary
Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. 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. Pharmacogenetics may improve health outcomes by allowing clinicians to tailor medications to patients’ individual genetic profiles. Tamoxifen reduces breast cancer recurrence [4] and mortality [5,6] among women with hormone receptor-positive breast cancer. Tamoxifen reduces the risk of breast cancer in high risk women [7]. Cytochrome P450 2D6 enzyme (CYP2D6) is the rate-limiting enzyme that converts N-desmethyl-tamoxifen into endoxifen [10,12,13]
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