Therapeutic Drug Monitoring-Guided Adjuvant Tamoxifen Dosing in Patients with Early Breast Cancer: A Cost-Effectiveness Analysis from the Prospective TOTAM Trial

Clin Drug Investig. 2022 Feb;42(2):163-175. doi: 10.1007/s40261-021-01114-6. Epub 2022 Jan 12.


Background and objectives: Endoxifen is the active metabolite of tamoxifen, and a minimal plasma concentration of 16 nM has been suggested as a threshold above which it is effective in reducing the risk of breast cancer recurrence. The aim of the current analysis was to investigate the cost-effectiveness of therapeutic drug monitoring (TDM)-guided tamoxifen dosing.

Methods: A cost-effectiveness analysis was performed from a Dutch healthcare perspective, using a partitioned survival model and a lifetime horizon. The reduction in subtherapeutic treatment following TDM is modelled as improved rates of recurrence-free survival (RFS) and overall survival (OS) in comparison to standard tamoxifen treatment. A probabilistic sensitivity analysis (PSA) and a series of scenario analyses were performed to assess the robustness of the results.

Results: Base-case results estimated a total increase in life years and quality-adjusted life years (QALYs) for TDM of 0.40 and 0.53, respectively. Total costs for TDM and standard tamoxifen treatment are €32,893 and €39,524, respectively. The TDM intervention results in both more QALYs and less healthcare costs, indicating a dominating effect for TDM. The PSA results indicate that the probability of TDM being cost-effective is 92% when using a willingness-to-pay threshold of €20,000.

Conclusions: TDM-guided dose optimization of tamoxifen is estimated to save costs and increase QALYs for early breast cancer patients.

Publication types

  • Clinical Trial

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Cost-Benefit Analysis
  • Drug Monitoring
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Prospective Studies
  • Quality-Adjusted Life Years
  • Tamoxifen


  • Tamoxifen