We have previously reported an association between ABCB1 C3435T polymorphism and docetaxel pharmacokinetics in breast cancer patients. We therefore investigated whether these parameters could account for variations in pathological response. Five ABCB1 polymorphisms including C3435T polymorphism were analyzed in breast cancer patients receiving neoadjuvant chemotherapy with doxorubicin and docetaxel (n = 101). Pathological response was assessed using the Sataloff classification. Pharmacokinetic analysis was performed for the first course of docetaxel (n = 84). No significant association was found between ABCB1 polymorphisms or docetaxel pharmacokinetics and pathological complete response. C3435T genotype was an independent predictive factor of good response in breast (response >50 %, i.e., Sataloff T-A and T-B): OR: 4.6 (95 % CI: 1.3–16.1), p = 0.015, for TT patients versus CT and CC patients. Area under the plasma concentration–time curve (AUC) of docetaxel was the only independent predictive factor of the total absence of response in breast (Sataloff T-D): OR: 14.3, (95 % CI: 1.7–118), p = 0.015, for AUC of docetaxel <3,500 μg h/L versus ≥3,500 μg h/L. These results suggest that C3435T polymorphism and docetaxel exposure are involved in the response to neoadjuvant chemotherapy in breast cancer patients and may be useful to optimize individualized therapy.
Breast cancer Docetaxel pharmacokinetics and pharmacodynamics ABCB1 Polymorphisms Pharmacogenomics Drug resistance Neoadjuvant Chemotherapy
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The authors would like to thank Assistance Publique-Hôpitaux de Paris and ACTT (Amis du Centre des Tumeurs de Tenon) association for financial support, URC-Est for help in the design of this study, and Jean-Pierre Lotz, Florent Soubrier and Serge Uzan for their constant support. This study was supported by Assistance Publique-Hôpitaux de Paris (Grant Number PHRC AOR03015) and ACTT (Amis du Centre des Tumeurs de Tenon) association.
Conflict of interest
The authors declare that they have no conflict of interest.
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