Tamoxifen is the current standard treatment of choice for ER+ breast cancer treatment. It works by binding to the estrogen receptor; the drug is metabolized to endoxifen (4-hydroxy-N-desmethyl tamoxifen), which has proven to be an important contributor to overall anticancer effect. Endoxifen is formed predominantly by CYP2D6 from N-desmethyl tamoxifen, the most abundant metabolite.
Patients with tamoxifen metabolite levels lower than 5.97 ng/mL have been found to have a 30% higher chance of experiencing breast cancer recurrence. Predictors for high risk of breast cancer recurrence include lower tamoxifen concentrations caused by a poor/intermediate metabolizer genotype.
Nalagenetics is working with a private hospital in Indonesia to test the tamoxifen metabolite levels of 200 patients diagnosed with ER+ breast cancer. We deployed pharmacogenetic tests targeting the CYP2D6 gene, the specific biomarker for tamoxifen metabolism.
According to Dutch Pharmacogenomics Working Group (DPWG) and Clinical Pharmacogenetics Implementation Consortium (CPIC), patients with 1 or more reduced-activity mutations on CYP2D6 gene are recommended to either take a higher dosage of tamoxifen or, to protect patients from adverse side effects, take aromatase inhibitors.
Patients who are found to have genetic profiles indicating poor tamoxifen metabolism at the private hospital were given personalized therapy. Afterwards doctors compared the active metabolite levels before and after dose adjustment.
Download our factsheet to learn more about pharmacogenetics in cancer.
