Pharmacogenetic Approach to Toxicity in Breast Cancer Patients Treated with Taxanes

Abstract

Background: Taxanes are widely used to treat breast cancer patients. Taxanes are metabolized in human liver by the cytochrome CYP3A and are substrate of ATP-binding cassette multidrug transporters ABCB1. Single-nucleotide polymorphisms (SNPs) in genes involved in taxanes' metabolism could affect the inter-individual variability in reported toxicities.

Materials and methods: In this retrospective study, 152 women, affected by breast cancer and receiving a taxane-based chemotherapy, were enrolled. A peripheral blood sample was taken for genotyping the following polymorphisms: CYP3A4* 1B (A>G), CYP3A5 *3 (G>A) and ABCB1 (C1236T; C3435T).

Results: We observed an association between ABCB1 3435 T/T and lower grade of toxicities (p=0.05). No other association were found for CYP 3A4 *1B, 3A5*3 and ABCB1 C1236T.

Conclusion: ABCB1 3435 T/T seems to be associated to lower rate of toxicity in patients receiving taxanes. Further prospective and larger studies should be performed to clarify the role of this polymorphism.

Keywords: ABCB1; Breast cancer; P-gp; cytochrome P450; polymorphisms; taxanes.