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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)995-999
Number of pages5
JournalCancer Science
Volume99
Issue number5
DOIs
Publication statusPublished - 01-05-2008
Externally publishedYes

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Cytochrome P-450 CYP2D6
Tamoxifen
Breast Neoplasms
Recurrence
Survival
Alleles
Therapeutics
Genotype
Confidence Intervals
Cytochrome P-450 Enzyme System
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kiyotani, K., Mushiroda, T., Sasa, M., Bando, Y., Sumitomo, I., Hosono, N., ... Zembutsu, H. (2008). Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. Cancer Science, 99(5), 995-999. https://doi.org/10.1111/j.1349-7006.2008.00780.x
Kiyotani, Kazuma ; Mushiroda, Taisei ; Sasa, Mitsunori ; Bando, Yoshimi ; Sumitomo, Ikuko ; Hosono, Naoya ; Kubo, Michiaki ; Nakamura, Yusuke ; Zembutsu, Hitoshi. / Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. In: Cancer Science. 2008 ; Vol. 99, No. 5. pp. 995-999.
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Kiyotani, K, Mushiroda, T, Sasa, M, Bando, Y, Sumitomo, I, Hosono, N, Kubo, M, Nakamura, Y & Zembutsu, H 2008, 'Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy', Cancer Science, vol. 99, no. 5, pp. 995-999. https://doi.org/10.1111/j.1349-7006.2008.00780.x

Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. / Kiyotani, Kazuma; Mushiroda, Taisei; Sasa, Mitsunori; Bando, Yoshimi; Sumitomo, Ikuko; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Zembutsu, Hitoshi.

In: Cancer Science, Vol. 99, No. 5, 01.05.2008, p. 995-999.

Research output: Contribution to journalArticle

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T1 - Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy

AU - Kiyotani, Kazuma

AU - Mushiroda, Taisei

AU - Sasa, Mitsunori

AU - Bando, Yoshimi

AU - Sumitomo, Ikuko

AU - Hosono, Naoya

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Zembutsu, Hitoshi

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Y1 - 2008/5/1

N2 - 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.

AB - 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.

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