title: Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy.
abstract: The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. We investigated the predictive value of the CYP2D6*10 allele, which decreased CYP2D6 activity, for clinical outcomes of patients that received adjuvant tamoxifen monotherapy after surgical operation on breast cancer. Among 67 patients examined, those homozygous for the CYP2D6*10 alleles revealed a significantly higher incidence of recurrence within 10 years after the operation (P = 0.0057; odds ratio, 16.63; 95% confidence interval, 1.75-158.12), compared with those homozygous for the wild-type CYP2D6*1 alleles. The elevated risk of recurrence seemed to be dependent on the number of CYP2D6*10 alleles (P = 0.0031 for trend). Cox proportional hazard analysis demonstrated that the CYP2D6 genotype and tumor size were independent factors affecting recurrence-free survival. Patients with the CYP2D6*10/*10 genotype showed a significantly shorter recurrence-free survival period (P = 0.036; adjusted hazard ratio, 10.04; 95% confidence interval, 1.17-86.27) compared to patients with CYP2D6*1/*1 after adjustment of other prognosis factors. The present study suggests that the CYP2D6 genotype should be considered when selecting adjuvant hormonal therapy for breast cancer patients.
authors.affiliation: Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo 108-8639, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sumitomo
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6