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

  • Preclinical study
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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.

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Abbreviations

ER:

Estrogen receptor

PgR:

Progesterone

CYP2D6:

Cytochrome P450 2D6

AIs:

Aromatase inhibitors

RFS:

Recurrence free survival

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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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Authors and Affiliations

  1. Center for Breast Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Korea

    In Hae Park, Jungsil Ro, Keun Seok Lee, Han Sung Kang, So-Youn Jung & Seeyeon Lee

  2. Cancer Biostatistics Branch, Division of Cancer Epidemiology and management, National Cancer Center, Gyeonggi-do, Korea

    Sohee Park

  3. Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea

    Hyeong-Seok Lim

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  1. In Hae Park
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  2. Jungsil Ro
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  3. Sohee Park
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Correspondence to Jungsil Ro.

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Park, I.H., Ro, J., Park, S. et al. Lack of any association between functionally significant CYP2D6 polymorphisms and clinical outcomes in early breast cancer patients receiving adjuvant tamoxifen treatment. Breast Cancer Res Treat 131, 455–461 (2012). https://doi.org/10.1007/s10549-011-1425-2

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  • DOI: https://doi.org/10.1007/s10549-011-1425-2

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