Endoxifen Levels and Metabolic Phenotype-Associated Factors in Mexican Mestizo Patients Under Tamoxifen Treatment

Abstract

Aim: To evaluate plasma endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment. Patients & methods: A total of 138 breast cancer patients under tamoxifen treatment were cross-sectionally evaluated and side effects (SE) were recorded. CYP2D6 genetic phenotypes (GP) and metabolic phenotypes (MP) were assessed (metabolic poor [mPM], intermediate [mIM], normal [mNM], and ultrarapid [mUM] metabolizer). Associations were tested in uni-multivariate models for endoxifen >5.9 ng/ml and for mNM + mUM MP. Results: The main SE was hot flashes (62%). Distribution of the CYP2D6 MP was 4.3% mPM; 14.5% mIM; 75.4% mNM; and 5.8% mUM. Endoxifen >5.9 ng/ml was partially associated with SE (p = 0.06); the mNM + mUM MP was associated with treatment time (p = 0.03). Conclusion: The endoxifen-associated factors in Mexican Mestizo patients remain inconclusive, although treatment time was associated with MP.

Keywords::

• breast cancer
• CYP2D6
• endoxifen
• metabolic phenotype
• Mexican Mestizos
• tamoxifen

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2020-0061

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JA Rangel-Méndez. The first draft of the manuscript was written by JA Rangel-Méndez and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. JA Rangel-Méndez collected information, performed molecular, analytical and statistical analyses and wrote the first paper draft; R Rubi-Castellanos assisted molecular analyses and reviewed final the final version of paper; RE Moo-Puc submitted original project for financial sponsorship, revised final manuscript and acted as corresponding author.

Acknowledgments

The authors would like to thanks the UMAE Oncology Department for allowing patient invitation and the UMAE Medical Record-Storage Department for clinical file revision. RE Moo-Puc thanks Fundación IMSS AC by the use of the ‘Centro de Investigación en Salud Dr Jesús Kumate Rodríguez’ facilities. The authors also thanks M Graniel-Sabido, L Arciga-Moreno and L Ku-Canto for their invaluable assistance with sample processing. J Lindsay-Edwards assisted with manuscript editing.

Financial & competing interests disclosure

This research was supported by the Instituto Mexicano del Seguro Social (project no. FIS/IMSS/PROT/PRIO/15/044). 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

Informed consent was obtained from all individual participants included in the study. All procedures complied with the ethical standards of the IMSS National Clinical Research Ethics Committee (R-2013-785-057), the Dr. Hideyo Noguchi Regional Research Center Review Board for Ethical Research with Human Subjects and the 1964 Helsinki Declaration and its amendments.

Availability of data & materials

Database is available upon request.

Additional information

Funding

This research was supported by the Instituto Mexicano del Seguro Social (project no. FIS/IMSS/PROT/PRIO/15/044). 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.