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 ATPbinding cassette multidrug transporters ABCB1. Singlenucleotide 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.