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. Cancer 2009;115:952-61. (c) 2009 American Cancer Society.