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Polymorphismes et traitements néoadjuvants des cancers du sein : efficacité du docétaxel et polymorphisme d'ABCB1/MDR1

Abstract : In non-metastatic breast cancer, neoadjuvant treatment allows to study the parameters influencing their effectiveness, related to the tumor and / or the host. The MDR family proteins, especially ABCB1 are involved in the mechanisms of resistance to anthracyclines and taxanes. The correlations between efficiency (histological response), ABCB1 polymorphism (patients and tumors) and pharmacokinetics of doxorubicin and docetaxel have been studied in the context of a therapeutic trial. In this study, polymorphism in exon 26 of ABCB1 (rs1045642) is the only that influences the pharmacokinetics of docetaxel and this only in premenopausal patients. Patients carrying CC genotype (40%) have an average value of the AUC of docetaxel significantly lower than those carrying genotypes CT (45%) and TT (15%) (p <0.0001). Moreover it was found in premenopausal patients a statistically significant correlation between low rates of docetaxel AUC and diplotype 2677GG-3435CC and 1236CC haplotype-61AA-2677GG-3435CC. It has not been found a link between ABCB1 polymorphisms and the pharmacokinetics of doxorubicin. There is also a negative relationship between AUC of docetaxel and pathological response. There seems therefore that a minimum value of AUC of docetaxel is necessary to obtain a response. Furthermore, we found an association between tumor response and polymorphism of ABCB1 (C3435T genotype, CT and TT vs. CC)
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https://tel.archives-ouvertes.fr/tel-00829467
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Submitted on : Monday, June 3, 2013 - 1:06:32 PM
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  • HAL Id : tel-00829467, version 1

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Joseph Gligorov. Polymorphismes et traitements néoadjuvants des cancers du sein : efficacité du docétaxel et polymorphisme d'ABCB1/MDR1. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PA066082⟩. ⟨tel-00829467⟩

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