Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 May;99(5):995-9.
doi: 10.1111/j.1349-7006.2008.00780.x. Epub 2008 Feb 24.

Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy

Kazuma Kiyotani  1 , Taisei Mushiroda, Mitsunori Sasa, Yoshimi Bando, Ikuko Sumitomo, Naoya Hosono, Michiaki Kubo, Yusuke Nakamura, Hitoshi Zembutsu
Affiliations

Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy

Kazuma Kiyotani et al. Cancer Sci. 2008 May.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of recurrence‐free survival rate for patients with the CYP2D6*10 genotype. (a) Comparison among CYP2D6*1/*1, *1/*10 and *10/*10 patients. (b) Comparison between CYP2D6*1/*1 + *1/*10 and *10/*10 patients.
Figure 2
Figure 2
Annual hazard rates for recurrence‐free survival comparing patients with the CYP2D6*1/*1, *1/*10 and *10/*10 genotypes.
See this image and copyright information in PMC

Comment in

References

    1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) . Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998; 351: 1451–67. - PubMed
    1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15‐year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–717. - PubMed
    1. Borgna JL, Rochefort H. Hydroxylated metabolites of tamoxifen are formed in vivo and bound to estrogen receptor in target tissues. J Biol Chem 1981; 256: 859–68. - PubMed
    1. Lien EA, Solheim E, Lea OA, Lundgren S, Kvinnsland S, Ueland PM. Distribution of 4‐hydroxy‐N‐desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res 1989; 49: 2175–83. - PubMed
    1. Johnson MD, Zuo H, Lee KH et al . Pharmacological characterization of 4‐hydroxy‐N‐desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85: 151–9. - PubMed