1. ¹Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
2. ²Siteman Cancer Center, St Louis, MO, USA
3. ³Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
4. ⁴Division of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Correspondence: Dr S Marsh, Washington University School of Medicine, Campus Box 8069, 660 S. Euclid Avenue, St Louis, MO 63110, USA. E-mail: smarsh@im.wustl.edu

⁵Current address: UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599, USA.

Received 8 July 2006; Revised 31 October 2006; Accepted 4 November 2006; Published online 16 January 2007.

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.