Tamoxifen Prediction Study in Patients With ER+ Breast Cancer

Adjuvant treatment with tamoxifen is the standard of care for women with estrogen receptor positive (ER+) breast cancer. Tamoxifen is converted to endoxifen, its active metabolite, via CYP2D6 enzymes. The literature states that an endoxifen concentration of at least 16 nmol/L is needed to produce a therapeutic effect (4). Therapeutic Drug Monitoring (TDM) has been proven to be a successful technique to reach the 16 nmol/L endoxifen threshold after 6 months. However, in general TDM can only be used when a drug is in steady-state, which for endoxifen is reached after 3 months for normal metabolizers. For poor- and intermediate metabolizers, the time until steady-state is presumably even longer. This could possibly result in undertreatment within the first 3 to 6 months of tamoxifen treatment. In this study, model-informed precision dosing (MIPD) will be used to counter this problem. The Pharmacokinetic-model, which is used for MIPD, includes CYP2D6 genotype, co-medication, age, body height, BMI and CYP2D6/CYP3A inhibitor use to predict a patient tailored dose. Using MIPD, our aim is to decrease the proportion of patients that are undertreated within the first three months of tamoxifen treatment.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

1. Age ≥ 18 years;
2. WHO Performance Status ≤ 1 (see Appendix A);
3. Patients with primary breast cancer, with a prescription for adjuvant tamoxifen treatment;
4. Willing to abstain from strong and moderate CYP3A4 or CYP2D6 inhibitors or inducers, according to: CYTOCHROME P450 DRUG INTERACTION TABLE - Drug Interactions (iu.edu);
5. Able and willing to sign the Informed Consent Form;
6. Able and willing to undergo blood sampling for PK analysis.

Exclusion Criteria:

1. Patients with known alcoholism, drug addiction and/or psychiatric or physiological condition which in the opinion of the investigator would impair treatment compliance;
2. \> 2 weeks of tamoxifen treatment before inclusion;
3. Patients who's endoxifen levels have been used for therapeutic drug monitoring in the past.