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Breast Cancer Research and Treatment

, Volume 131, Issue 2, pp 455–461 | Cite as

Lack of any association between functionally significant CYP2D6 polymorphisms and clinical outcomes in early breast cancer patients receiving adjuvant tamoxifen treatment

  • In Hae Park
  • Jungsil RoEmail author
  • Sohee Park
  • Hyeong-Seok Lim
  • Keun Seok Lee
  • Han Sung Kang
  • So-Youn Jung
  • Seeyeon Lee
Preclinical study

Abstract

Active metabolites of tamoxifen are formed mainly by the action of cytochrome P450 2D6 (CYP2D6). Since there are controversies regarding associations between CYP2D6 polymorphisms and outcomes among women with early breast cancer (EBC) treated with tamoxifen, the present evaluation of links with clinical outcomes was conducted. We analyzed a total of 716 patients treated with tamoxifen for hormone receptor positive EBC between 2001 and 2005 at the National Cancer Center, Korea. All patients received tamoxifen 20 mg/day for more than 6 months. DNA obtained from whole blood samples was genotyped for CYP2D6 variants associated with reduced (*10, *41) and absent (*5) activity. Of the total of 716 patients, 558 (77.9%) received adjuvant or neoadjuvant chemotherapy prior to the tamoxifen therapy. From the genotyping of CYP2D6, 152 (21.2%) patients were classified as having the wild type (W/W), 376 (52.7%) one variant allele (W/V), and 188 (26.1%) two variant alleles (V/V). Seventy (9.8%) patients experienced disease recurrence with a median follow-up of 5.6 (range, 0.6–10.3) years. Although known prognostic factors, including tumor size, nodal status, Ki67, PgR negativity, and HER2 positivity showed strong associations with the recurrence free survival (RFS) in this population, no significant association with any of the CYP2D6 genetic variants was evident (P = 0.61; hazard ratio [HR] = 1.14; 95% CI 0.68–1.92). This remained the case after subgroup analysis according to different adjuvant treatments. Polymorphisms of CYP2D6 were not associated with clinical outcomes in EBC patients receiving adjuvant tamoxifen treatment.

Keywords

CYP2D6 Polymorphism Tamoxifen Breast cancer 

Abbreviations

ER

Estrogen receptor

PgR

Progesterone

CYP2D6

Cytochrome P450 2D6

AIs

Aromatase inhibitors

RFS

Recurrence free survival

Notes

Acknowledgments

This study was supported by NCC Grant 0910320.

Conflicts of interest

The authors declared that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • In Hae Park
    • 1
  • Jungsil Ro
    • 1
    Email author
  • Sohee Park
    • 2
  • Hyeong-Seok Lim
    • 3
  • Keun Seok Lee
    • 1
  • Han Sung Kang
    • 1
  • So-Youn Jung
    • 1
  • Seeyeon Lee
    • 1
  1. 1.Center for Breast CancerNational Cancer CenterGyeonggi-doKorea
  2. 2.Cancer Biostatistics Branch, Division of Cancer Epidemiology and managementNational Cancer CenterGyeonggi-doKorea
  3. 3.Department of Clinical Pharmacology and Therapeutics, College of MedicineUniversity of Ulsan, Asan Medical CenterSeoulKorea

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