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

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 tamo...

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Bibliographic Details
Published in:Cancer 2009-03, Vol.115 (5), p.952-961
Main Authors: Okishiro, Masatsugu, Taguchi, Tetsuya, Jin Kim, Seung, Shimazu, Kenzo, Tamaki, Yasuhiro, Noguchi, Shinzaburo
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Agents, Hormonal - therapeutic use
Aryl Hydrocarbon Hydroxylases - genetics
Asian Continental Ancestry Group - genetics
Bone Density
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Chemotherapy, Adjuvant
Cholesterol - metabolism
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6 - genetics
Disease-Free Survival
Endometrium - pathology
Female
Genotype
Humans
Middle Aged
Neoplasms, Hormone-Dependent - drug therapy
Polymorphism, Genetic
Prognosis
Tamoxifen - therapeutic use
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Summary: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. 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. 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. 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.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.24111