Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen.
BACKGROUND
The authors investigated the impact of the genetic polymorphisms cytochrome P450 (CYP) family 2, subfamily D, polypeptide 6, allele 10 (CYP2D6 10) and CYP family 2, subfamily C, polypeptide 19, allele 2, 3 (CYP2C19 2, 3) on disease recurrence in patients with breast cancer who received adjuvant tamoxifen and evaluated the impact of those polymorphisms on endometrial thickness, bone mineral density (BMD), and serum total cholesterol levels.


METHODS
Patients with primary breast cancer (n=173) who had hormone receptor-positive tumors and who also received adjuvant tamoxifen were included in the current study. Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 were analyzed.


RESULTS
Recurrence-free survival (RFS) rates did not differ significantly between patients with the CYP2D6 10/10 genotype (n=40) and patients with the CYP2D6 wild-type (wt)/wt or wt/10 genotype (n=133) or between patients with the CYP2C19 2/2, 2/3, or 3/3 genotypes (n=41) and patients with the CYP2C19 wt/wt, wt/2, or wt/3 genotype (n=132). Multivariate analysis indicated that, even after adjustment for well established prognostic factors, these CYP2D6 or CYP2C19 genotypes were not associated significantly with the RFS rate. Moreover, these genotypes did not affect endometrial thickness, BMD, or total cholesterol levels 1 year after the start of tamoxifen treatment.


CONCLUSIONS
Neither the CYP2D6 10/10 genotype nor the CYP2C19 genotype is likely to have a clinically significant impact on prognosis, endometrial thickness, BMD, or total cholesterol levels in Japanese patients with breast cancer who are treated with adjuvant tamoxifen.
Okishiro
Masatsugu
M
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Taguchi
Tetsuya
T
Jin Kim
Seung
S
Shimazu
Kenzo
K
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015519:Bone Density; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002784:Cholesterol / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018572:Disease-Free Survival; D004717:Endometrium / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D002784:Cholesterol; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6