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Individualized Hormonal Therapy in Patients with Breast Cancer

Mariya Levkova, Dimitrina Konstantinova, Tanya Kadiyska, Ivan Donev

Abstract

Introduction: Tamoxifen is a selective estrogen receptor modulator (SERM) which is used in the treatment and prevention of breast cancer. It is a standard therapy for breast cancer in women.

The CYP2D6 is one of the main enzymes responsible for converting tamoxifen into its major active metabolite, endofixen. Variants in the CYP2D6 allele may lead to reduced or absent  enzyme activity. Individuals who carry these variant alleles may have reduced plasma concentrations of endoxifen and be  intermediate or poor metabolizers. That is why it is recommended to study the CYP2D6 genotypic heterogeneity before administering tamoxifen in order to provide an individualized hormonal therapy of breast cancer.

Aromatase inhibitors are a class of drugs, which block the enzyme aromatase and are used in the treatment of breast cancer in postmenopausal women. Aromatase catalyzes the last steps of estrogen biosynthesis and it  is a cytochrome P450 enzyme complex that is encoded by CYP19. Variants in CYP19A1 may be important, regarding both the efficacy and toxicity of aromatase inhibitors.

Materials and Methods: We tested 4 women for CYP2D6 genotypic heterogeneity and 2 for CYP19A1 genetic variations. All of them  had beeen diagnosed histologically  with estrogen – and progesterone – receptor - positive breast cancer.

We used PCR amplification method and Sanger sequencing.

Results: One of the patients was an intermediate tamoxifen metabolizer, one of the patients was a heterozygous carrier for CYP19A1 genetic variations.

Conclusions: It is of great significance for the treatment of breast cancer to test patients for their drug metabolism activity in order to provide a personalised approach in treating breast cancer.


Keywords

genetics, breast cancer, treatment


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