Tamoxifen and CYP2D6
Tamoxifen is activated by CYP2D6 into endoxifen, its most potent anti-oestrogen metabolite. Poor metabolisers have lower endoxifen levels, and several studies associate this with a higher breast-cancer recurrence rate.
Why does CYP2D6 matter for Tamoxifen?
Tamoxifen is activated by CYP2D6 into endoxifen, its most potent anti-oestrogen metabolite. Poor metabolisers have lower endoxifen levels, and several studies associate this with a higher breast-cancer recurrence rate. CYP2D6 metabolises around a quarter of all prescribed drugs, among them codeine, tramadol, tamoxifen, many antidepressants and antipsychotics, and some beta-blockers. It is the most polymorphic of the drug-metabolising enzymes: more than 100 star alleles are described, whole-gene deletions and duplications are common, and activity ranges from none to several times normal. Codeine is the classic example — the enzyme turns it into morphine, so poor metabolisers get little pain relief and ultrarapid metabolisers can be harmed by a standard dose.
What does CPIC recommend for each CYP2D6 phenotype on Tamoxifen?
The guidance below is the CPIC recommendation for prescribers, reproduced for reference. It is written for a clinician who knows the whole picture — never start, stop or change a medicine on the basis of this page.
| Phenotype | CPIC-based guidance |
|---|---|
| Ultrarapid Metabolizer | Standard tamoxifen dosing. Normal to increased conversion to endoxifen. |
| Normal Metabolizer | Standard tamoxifen dosing. |
| Intermediate Metabolizer | Consider higher dose tamoxifen (40mg) or alternative (aromatase inhibitor in postmenopausal women). |
| Poor Metabolizer | Avoid tamoxifen. Use aromatase inhibitor (postmenopausal) or alternative endocrine therapy. Insufficient conversion to endoxifen. |
Which CYP2D6 alleles decide the phenotype?
The phenotype is read from the two CYP2D6 star alleles a person carries. The full allele table, with the defining variants and their population frequencies, is on the CYP2D6 gene page.
Consumer DNA chips read single-nucleotide changes but cannot see gene deletions (*5) or duplications (*1xN, *2xN), which are exactly what defines many poor and ultrarapid metabolisers. A CYP2D6 call from chip data is therefore a lower-confidence estimate than for CYP2C19 or CYP2C9, and Orviva reports it with that caveat.
Other drugs affected by CYP2D6
- Codeine — Opioid Analgesic
- Tramadol — Opioid Analgesic
- Atomoxetine — ADHD Medication
- Ondansetron — Antiemetic
Upload your raw DNA file and see your metaboliser status → · Ask G2: “Does my CYP2D6 genotype affect Tamoxifen?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.