Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment.
BACKGROUND
Human cytochrome P450 2D6 (CYP2D6) genotype may affect the efficacy of tamoxifen treatment in Caucasian women with breast cancer. The most common polymorphism of CYP2D6 in Chinese women is variant 10 (188 C to T).


METHODS
Tamoxifen and 4-hydroxytamoxifen (4OHtam) were measured in the serum of 37 women with breast cancer who were receiving tamoxifen treatment. The association between CYP2D6 *10 genotype and survival was determined in a cohort of 293 women with breast cancer who received tamoxifen (n = 152) or who did not (n = 141).


RESULTS
The serum 4OHtam concentrations were significantly lower in women with the CYP2D6 *10 homozygous variant T/T genotype than in those with the homozygous wild-type C/C genotype (P = 0.04). Among tamoxifen-treated women, women with the T/T genotype had a significantly worse disease-free survival (DFS) than those with the C/C or C/T genotype, and the T/T genotype remained an independent prognostic factor of DFS in multivariate analysis (hazard ratio = 4.7; 95% confidence interval = 1.1-20.0; P = 0.04). Among women who did not receive tamoxifen, there was no significant association between CYP2D6 *10 genotype and survival.


CONCLUSIONS
In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome.
Xu
Y
Y
Breast Center.
Sun
Y
Y
Department of Traditional Chinese Medicine, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China.
Yao
L
L
Breast Center.
Shi
L
L
Breast Center.
Wu
Y
Y
Breast Center.
Ouyang
T
T
Breast Center.
Li
J
J
Breast Center.
Wang
T
T
Breast Center.
Fan
Z
Z
Breast Center.
Fan
T
T
Breast Center.
Lin
B
B
Breast Center.
He
L
L
Department of Biochemistry and Molecular Biology, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China.
Li
P
P
Department of Traditional Chinese Medicine, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China. Electronic address: zlxyt2@bjmu.edu.cn.
Xie
Y
Y
Breast Center.
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000097:blood / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C016601:afimoxifene; D019389:Cytochrome P-450 CYP2D6