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Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer

The Pharmacogenomics Journal volume 7, pages 362–365 (2007)Cite this article

Abstract

Paclitaxel is commonly used in the treatment of breast cancer. Variability in paclitaxel clearance may contribute to the unpredictability of clinical outcomes. We assessed genomic DNA from the plasma of 93 patients with high-risk primary or stage IV breast cancer, who received dose-intense paclitaxel, doxorubicin and cyclophosphamide. Eight polymorphisms in six genes associated with metabolism and transport of paclitaxel were analyzed using Pyrosequencing. We found no association between ABCB1, ABCG2, CYP1B1, CYP3A4, CYP3A5 and CYP2C8 genotypes and paclitaxel clearance. However, patients homozygous for the CYP1B1*3 allele had a significantly longer progression-free survival than patients with at least one Valine allele (P=0.037). This finding could reflect altered paclitaxel metabolism, however, the finding was independent of paclitaxel clearance. Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele.

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Acknowledgements

We thank A Garsa for technical assistance with this project. This work was supported by CA 33572, CA 62505 (Duarte) and the Pharmacogenetics Research Network U01 GM63340 (St Louis).

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Author notes

  1. H L McLeod

    Present address: UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, 27599, USA

Authors and Affiliations

  1. Department of Medicine,

    S Marsh, X Li, C R King, W D Shannon & H L McLeod

  2. Washington University School of Medicine, St Louis, MO, USA

    S Marsh, X Li, C R King, W D Shannon & H L McLeod

  3. Siteman Cancer Center, St Louis, MO, USA

    S Marsh, W D Shannon, H L McLeod & T W Synold

  4. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    G Somlo

  5. Division of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    P Frankel

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Correspondence to S Marsh.

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Marsh, S., Somlo, G., Li, X. et al. Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 7, 362–365 (2007). https://doi.org/10.1038/sj.tpj.6500434

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