Association Between CYP2D6 Genotypes and the Clinical Outcomes of Adjuvant Tamoxifen for Breast Cancer: A Meta-Analysis

Abstract

Aim: Tamoxifen is one of the most commonly used endocrine therapeutic agents for breast cancer. Although many studies have examined whether the treatment outcomes of tamoxifen for breast cancer differ according to CYP2D6 genotype, the study results have been inconsistent, and the role of CYP2D6 in the prediction of patient outcomes from tamoxifen therapy remains controversial. This study evaluated the association between CYP2D6 genotypes and postoperative tamoxifen treatment outcome in patients with breast cancer, using the available previous study results. Materials & methods: We performed a meta-analysis of ten previous clinical reports (n = 5183) to evaluate the association between CYP2D6 genotype and hazard ratios for the recurrence risk of breast cancer after postoperative tamoxifen treatment. Pooled estimates of hazard ratios were computed using R and NONMEM^® software. Results: A significantly increased risk of breast cancer recurrence in patients carrying variant CYP2D6 genotypes was found in this investigation. The mean hazard ratios and 95% CI were 1.60 (1.04–2.47) in the random effect model implemented in R and 1.63 (1.01–2.62) in the random effect model in NONMEM. The bootstrap result (2000 replicates) of NONMEM was 1.64 (1.07–2.79). Conclusion: Our present findings suggest that genetic polymorphisms of CYP2D6 may be important predictors of the clinical outcomes of adjuvant tamoxifen treatment for the patients with breast cancer. A large-scale, prospective, randomized, well-controlled trial is warranted to confirm our findings.

Original submitted 23 July 2013; Revision submitted 30 September 2013

KEYWORDS::

• adjuvant
• breast cancer
• CYP2D6
• hazard ratio
• recurrence risk
• tamoxifen

Financial & competing interests disclosure

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (A070001) and a grant (2008-440) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. 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 apart from those disclosed.No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (A070001) and a grant (2008-440) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. 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 apart from those disclosed.No writing assistance was utilized in the production of this manuscript.