CYP2D6 polymorphisms and tamoxifen adverse effects

CYP2D6 polymorphisms and tamoxifen adverse effects - Video Abstract ID 126557

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Video abstract of original research paper “CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study” published in the open access journal Breast Cancer - Targets and Therapy by authors Wickramage I, Tennekoon KH, Ariyaratne MAY.

Introduction and aims: Tamoxifen is an adjuvant drug effective in treating hormone receptor – positive breast cancer. However, 30%–50% of patients relapse and many develop adverse
effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little
evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects,
hitherto not studied in Sri Lanka.
Methods: A retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka.
They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their
blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP) assay.
Results: SNP/allele frequencies detected: 1846G greater than A (confirmatory of *4 null allele)=8.3%; 2549delA (confirmatory of *3 null allele)=50%; 100C greater than T (suggestive of *10 reduced functional allele, in addition to other alleles)=0%; combination of 2988G greater than A, -1584C and 2850C greater than T (strongly suggestive of *41 or other reduced functional allele)=4.8%. Occurrence of heterozygous 2988G greater than A SNP with -1584C and 2850C greater than T was significantly higher among those with ultrasound-diagnosed fatty liver following the commencement of tamoxifen therapy (P=0.029). Adverse effects occurred at a significantly higher frequency among postmenopausal women (P=0.041). Three patients who developed recurrence of breast cancer had no association with SNPs tested.
Conclusions: CYP2D6 SNP combination 2988G greater than A, -1584C and 2850C greater than T, strongly suggestive of *41 reduced functional allele, is likely to be useful in predicting occurrence of adverse effect fatty liver in breast cancer patients on tamoxifen, thereby alternative treatment can be considered and lifestyle modifications implemented. Larger sample studies are recommended with the measurement of tamoxifen and metabolite levels. Alternative therapy should be considered for postmenopausal patients.

Read the Original Research paper here https://doi.org/10.2147/BCTT.S126557

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