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The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

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Abstract

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan–Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57–109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79–23.2) compared to those without this combination which was 48 months (95% CI = 14.7–81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.

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ACKNOWLEDGEMENTS

This research is supported by a grant from the Ministry of Science, Technology and Innovation Malaysia (Grant no: 02-01-01-SF0173). We thank the director general of Ministry of Health Malaysia, Suzana Ismail and Khairussaleh Jalaludin for the approval and assistance in collection of patients’ samples.

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Authors and Affiliations

  1. Pharmacogenomics Centre (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Campus Puncak Alam, 42300, Puncak Alam, Selangor Darul Ehsan, Malaysia

    L. K. Teh, N. I. Mohamed, M. Z. Salleh & J. K. S. Shia

  2. Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia

    M. Rohaizak, N. S. Shahrun & J. J. Saladina

  3. UKM Medical Biology Institute (UMBI) and Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, (UKMMC), Kuala Lumpur, Malaysia

    H. Roslan

  4. Faculty of Medicine, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor Darul Ehsan, Malaysia

    S. Sood

  5. Department of Surgery, Selayang Hospital, Kuala Lumpur, Malaysia

    T. S. Rajoo, S. P. Muniandy & G. Henry

  6. Department of Internal Medicine, Kulliyah of Medicine, International Islamic University Malaysia (IIUM)/Tengku Ampuan Afzan Hospital (HTAA), Pahang Darul Makmur, Malaysia

    H. A. Ngow

  7. Department of Surgery, International Islamic University Malaysia (IIUM), Pahang Darul Makmur, Malaysia

    K. T. Hla U & J. Din

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  1. L. K. Teh
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  2. N. I. Mohamed
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  14. K. T. Hla U
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  15. J. Din
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Correspondence to L. K. Teh.

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Teh, L.K., Mohamed, N.I., Salleh, M.Z. et al. The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1 . AAPS J 14, 52–59 (2012). https://doi.org/10.1208/s12248-011-9313-6

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  • DOI: https://doi.org/10.1208/s12248-011-9313-6

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