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. 2010 Aug 10;103(4):560-6.
doi: 10.1038/sj.bjc.6605789. Epub 2010 Jul 13.

Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients

A Fajac  1 , J Gligorov, K Rezai, P Lévy, E Lévy, F Selle, K Beerblock, D Avenin, P Saintigny, S Hugonin, J-F Bernaudin, F Lokiec
Affiliations

Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients

A Fajac et al. Br J Cancer. .

Abstract

Background: It can be hypothesised that inherited polymorphisms in the drug-transporter ABCB1 gene may interfere with interindividual variations in drug response in breast cancer patients. Docetaxel is a substrate for ABCB1 whose function has been shown to be modulated by oestrogen and progesterone.

Methods: Whether ABCB1 polymorphisms including T-129C, A61G, C1236T, G2677T/A and C3435T polymorphisms could account for variations in the disposition of docetaxel and whether menopausal status at the time of diagnosis might interact with this effect were analysed in women receiving neoadjuvant chemotherapy for breast cancer (n=86).

Results: A highly significant association was observed, but restricted to premenopausal women (n=53), between the pharmacokinetics of docetaxel and C3435T polymorphism, as patients with CC genotype had lower mean values of the area under the plasma concentration-time curve (AUC) of docetaxel than patients with CT and TT genotypes (P<0.0001). Comparison between pre- and postmenopausal women with the same C3435T genotype yielded a significant difference in docetaxel AUC only for CC genotype (P<0.0001).

Conclusion: These results suggest that C3435T polymorphism genotyping and menopausal status at the time of diagnosis might be useful when considering chemotherapy regimens including docetaxel in breast cancer patients.

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Figures

Figure 1
Figure 1
The aera under the plasma concentration-time curve (AUC) of docetaxel according to C3435T polymorphism and menopausal status. In (A) exclusion of the outlier patient with an AUC >34 000 μg h l–1 did not alter the P-value. (A) Premenopausal patients. (B) Postmenopausal patients.
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