title: Influence of ABCB1 polymorphisms and docetaxel pharmacokinetics on pathological response to neoadjuvant chemotherapy in breast cancer patients.
abstract: 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.
authors.affiliation: Département de Santé Publique, hôpital Tenon, AP-HP, Inserm UMR S 707, Université Pierre et Marie Curie, 4 rue de la Chine, 75020, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lévy
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.forename: Keyvan
authors.initials: K
authors.lastname: Rezai
authors.forename: Eric
authors.initials: E
authors.lastname: Lévy
authors.forename: Frédéric
authors.initials: F
authors.lastname: Selle
authors.forename: Pierre
authors.initials: P
authors.lastname: Saintigny
authors.forename: François
authors.initials: F
authors.lastname: Lokiec
authors.forename: Danielle
authors.initials: D
authors.lastname: Avenin
authors.forename: Karine
authors.initials: K
authors.lastname: Beerblock
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lotz
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bernaudin
authors.forename: Anne
authors.initials: A
authors.lastname: Fajac
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D005838:Genotype; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D043823:Taxoids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel