Fajac A, Gligorov J, Rezai K, et al. Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients. Br J Cancer 2010 103(4):560-566.
doi 10.1038/sj.bjc.6605789
http://www.nature.com/bjc/journal/v103/n4/abs/6605789a.html
http://www.nature.com/bjc/journal/v103/n4/full/6605789a.html
http://www.nature.com/bjc/journal/v103/n4/pdf/6605789a.pdf
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Molecular Diagnostics
British Journal of Cancer (2010) 103, 560–566. doi:10.1038/sj.bjc.6605789 www.bjcancer.com
Published online 13 July 2010
Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients
A Fajac1, J Gligorov2, K Rezai3, P Lévy4, E Lévy5, F Selle2, K Beerblock2, D Avenin2, P Saintigny6, S Hugonin1, J-F Bernaudin1 and F Lokiec3
. 1Service d’Histologie-Biologie Tumorale, hôpital Tenon, AP-HP, ER2 UPMC Université Pierre et Marie Curie, 4 rue de la Chine, Paris 75020, France
. 2Service d’Oncologie, hôpital Tenon, AP-HP, 4 rue de la Chine, Paris 75020, France
. 3Service de Pharmacologie, Centre René Huguenin, 35 rue Dailly, St-Cloud 92210, France
. 4Département de Santé Publique, hôpital Tenon, AP-HP, Inserm UMR S 707, Université Pierre et Marie Curie, 4 rue de la Chine, Paris 75020, France
. 5Service d’Oncologie, HEGP, AP-HP, 20 rue Leblanc, Paris 75015, France
. 6Service d’Oncologie, Hôpital Avicenne, AP-HP, 125 rue Stalingrad, Bobigny 93000, France
Correspondence: Dr A Fajac, E-mail: anne.fajac@tnn.aphp.fr
Received 13 January 2010; Revised 14 June 2010; Accepted 16 June 2010; Published online 13 July 2010.
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.
Keywords: ABCB1; polymorphisms; docetaxel; pharmacokinetics; breast cancer
© 2010 Cancer Research UK