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Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy

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Abstract

Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95% CI 0.97–12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.

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Acknowledgments

This study was supported in part by Marshfield Clinic Research Foundation Disease Specific Restricted Funds. We thank Marshfield Clinic Research Foundation for its support through the assistance of Alice Stargardt in the preparation of this manuscript.

Conflict of interest

Dr. Flockhart serves on the scientific advisory board for Labcorp, the laboratory testing company, and had served as a paid consultant for Roche Molecular Diagnostics. Dr. Yan Jin is a full-time employee of Eli Lilly and Company. She is not involved in the raloxifene, arzoxifene or the oncology program.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI, 54476, USA

    Adedayo A. Onitilo

  2. Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Catherine A. McCarty & Ingrid Glurich

  3. Division of General Internal Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Russell A. Wilke

  4. Department of Hematology/Oncology, Marshfield Clinic, Marshfield, WI, USA

    Jessica M. Engel

  5. Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    David A. Flockhart, Anne Nguyen, Todd C. Skaar & Yan Jin

  6. Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Lang Li & Deming Mi

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  1. Adedayo A. Onitilo
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  2. Catherine A. McCarty
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Correspondence to Adedayo A. Onitilo.

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Onitilo, A.A., McCarty, C.A., Wilke, R.A. et al. Estrogen receptor genotype is associated with risk of venous thromboembolism during tamoxifen therapy. Breast Cancer Res Treat 115, 643–650 (2009). https://doi.org/10.1007/s10549-008-0264-2

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  • DOI: https://doi.org/10.1007/s10549-008-0264-2

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