Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.
BACKGROUND
Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated.


METHODS
In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism.


RESULTS
The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01).


CONCLUSIONS
Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.
Department of Medical Oncology, Çukurova University Medical School, Adana, Turkey.
Meral
M
Günaldı
Melek
M
Erkisi
Ciğdem Usul
CU
Afşar
Vehbi
V
Erçolak
Semra
S
Paydas
I Oguz
IO
Kara
Berksoy
B
Sahin
Umran Kucukgoz
UK
Gulec
Ata
A
Secilmis
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000000981:diagnostic imaging; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013629:Tamoxifen / Q000493:pharmacokinetics / Q000494:pharmacology*; D014421:Turkey; D014463:Ultrasonography; D044465:White People / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6