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Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer

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Abstract

Purpose

The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy.

Methods

A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients.

Results

The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity.

Conclusions

This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

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Acknowledgments

The authors would like to thank Dr. Joseph Simaan for reviewing and editing the manuscript. This study was funded by American University of Beirut Medical Practice Plan.

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, George Washington University, Washington, DC, USA

    F. Haroun

  2. Vascular Medicine Program, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    L. Al-Shaar & R. H. Habib

  3. Division of Hematology-Oncology, Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    N. El-Saghir, A. Tfayli, A. Bazarbachi, Z. Salem, A. Shamseddine & A. Taher

  4. Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig–Holstein, Kiel, Germany

    I. Cascorbi

  5. Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut, 1107 2020, Lebanon

    N. K. Zgheib

Authors
  1. F. Haroun
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  2. L. Al-Shaar
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  3. R. H. Habib
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  4. N. El-Saghir
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  6. A. Bazarbachi
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  8. A. Shamseddine
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  9. A. Taher
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  10. I. Cascorbi
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  11. N. K. Zgheib
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Corresponding author

Correspondence to N. K. Zgheib.

Additional information

F. Haroun and L. Al-Shaar made equal contribution.

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Haroun, F., Al-Shaar, L., Habib, R.H. et al. Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer. Cancer Chemother Pharmacol 75, 207–214 (2015). https://doi.org/10.1007/s00280-014-2632-4

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  • DOI: https://doi.org/10.1007/s00280-014-2632-4

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