Int J Med Sci 2013; 10(7):932-937. doi:10.7150/ijms.5708
Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer
1. Clinical Biochemistry Services, San Cecilio University Hospital. Avd/ Doctor Olóriz s/n 18012, Granada, Spain.
2. Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine Avd/Madrid s/n 18071, Granada, Spain.
3. Department of Oncology, San Cecilio University Hospital. Avd/Doctor Olóriz s/n 18012, Granada, Spain.
4. Aula de Estudios Avanzados. Fundación Tejerina. Madrid, Spain.
5. Department of Oncology, Hospital Provincial de Castellón. Avd/ Dr. Clará, nº 19, 12002 Castellón. Spain.
6. Molecular Biopathology Laboratory. Hospital Provincial de Castellón. Avd/ Dr. Clará, nº 19 12002. Castellón, Spain.
7. Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. Avd/Conocimiento s/n 18100 Armilla, Granada, Spain.
Background Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy.
Methods: We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography.
Results The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele *1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles.
Conclusion CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy.
Keywords: CYP2D6, CYP2C19, genetic diagnosis, estrogen-positive breast cancer, endoxifen, tamoxifen
Zafra-Ceres M, de Haro T, Farez-Vidal E, Blancas I, Bandres F, de Dueñas EM, Ochoa-Aranda E, Gomez-Capilla JA, Gomez-Llorente C. Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer. Int J Med Sci 2013; 10(7):932-937. doi:10.7150/ijms.5708. Available from http://www.medsci.org/v10p0932.htm