Abstract
PURPOSE: To examine the association between CYP2D6 genotype, discontinuation of tamoxifen therapy, and prognosis for breast cancer.
PATIENTS AND METHODS: We conducted a prospective-retrospective study linking data from a clinical breast cancer register, the Swedish Prescribed Drug Register, and self-reported questionnaires. We genotyped CYP2D6 in 1,309 patients with breast cancer who were treated with tamoxifen and were diagnosed from 2005 to 2012; they were categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. We investigated whether metabolizer status was associated with tamoxifen discontinuation and prognosis for breast cancer using Cox regression analysis.
RESULTS: The 6-month discontinuation rates of tamoxifen among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 7.1%, 7.6%, 6.7%, and 18.8%, respectively. A U-shaped association was found between CYP2D6 metabolizer status and breast cancer-specific mortality, with adjusted hazard ratios of 2.59 (95% CI, 1.01 to 6.67) for poor, 1.48 (95% CI, 0.72 to 3.05) for intermediate, 1 (reference) for normal, and 4.52 (95% CI, 1.42 to 14.37) for ultrarapid CYP2D6 metabolizers.
CONCLUSION: Both poor and ultrarapid CYP2D6 metabolizers of tamoxifen have a worse prognosis for breast cancer compared with normal metabolizers after receiving a standard dose of tamoxifen. This U-shaped association might call for individualized tamoxifen dosage.
Original language | English |
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Pages (from-to) | 548-557 |
Number of pages | 10 |
Journal | Journal of Clinical Oncology |
Volume | 38 |
Issue number | 6 |
Early online date | 4 Dec 2019 |
DOIs | |
Publication status | Published - 20 Feb 2020 |
Bibliographical note
Supported by Grants No. 2018-02547 from the Swedish Research Council, CAN 2016/684 from the Swedish Cancer Society, 2016-00081 and 2018-00877 from FORTE, and 20170088 from the Stockholm County Council.Keywords
- ADJUVANT HORMONE-THERAPY
- CLINICAL-OUTCOMES
- CYTOCHROME-P450 2D6
- ESTROGEN-RECEPTOR
- GENETIC POLYMORPHISMS
- HOT FLASHES
- METABOLISM
- PHARMACOGENETICS
- RISK-FACTORS
- WOMEN