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 study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy.
The question of whether genetic polymorphisms of CYP2D6 can affect treatment outcome in patients with early post-menopausal oestrogen receptor (ER)-positive breast cancer has been a matter of debate over the past few years.
Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009).
We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy.
The objective of this viewpoint is to highlight Therapeutic Drug Monitoring of endoxifen, the active tamoxifen metabolite, as the preferred methodology compared to CYP2D6 genotyping for individualizing tamoxifen therapy for ER-positive breast cancer patients treated in the adjuvant setting.
Critical appraisal of the literature provided evidence for the value of comprehensive CYP2D6 genotyping panels in guiding treatment decisions for non-metastatic ER-positive breast cancer patients.
Compared with a willingness-to-pay threshold of US$26,508/QALY in China, the CYP2D6*10 testing is the dominant strategy in postmenopausal women with ER-positive breast cancer in China, and the increased cost of genetic testing was completely worthwhile.