Recent advances in the personalized treatment of estrogen receptor-positive breast cancer with tamoxifen: a focus on pharmacogenomics

ABSTRACT

Introduction: Tamoxifen is still an important drug in hormone-dependent breast cancer therapy. Personalization of its clinical use beyond hormone receptor positivity could improve the substantial variability of the treatment response.

Areas covered: The overview of the current evidence for the treatment personalization using therapeutic drug monitoring, or using genetic biomarkers including CYP2D6 is provided. Although many studies focused on the PK aspects or the impact of CYP2D6 variability the translation into clinical routine is not clearly defined due to the inconsistent clinical outcome data.

Expert opinion: We believe that at least the main candidate factors, i.e. CYP2D6 polymorphism, CYP2D6 inhibition, endoxifen serum levels may become important predictors of clinical relevance for tamoxifen treatment personalization in the future. To achieve this aim, however, further research should take into consideration more precise characterization of the disease, epigenetic factors and also utilize an appropriately powered multifactorial approach instead of a single gene evaluating studies.

KEYWORDS:

• Breast cancer
• cytochrome P450
• endoxifen
• pharmacogenomics
• pharmacokinetics
• therapeutic drug monitoring

Article highlights

• Tamoxifen is still an important drug in hormone-dependent breast cancer therapy

• Several candidate genetic biomarkers including CYP2D6 have been evaluated as well as personalization via therapeutic drug monitoring

• Essential proof of evidence is still available neither for promising candidate genetic biomarkers nor for pharmacokinetic surrogates that would justify their current use in routine clinical settings

• Routine utilization of the biomarkers is not currently widely accepted in international therapeutic guidelines

• A few most promising candidate biomarkers are believed to prove their clinical utility in the future after their validation in upcoming research

This box summarizes key points contained in the article.

Declaration of interest

The authors were supported by Charles University (Progres Q25/LF1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.