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Breast Cancer Research and Treatment

, Volume 139, Issue 2, pp 421–428 | Cite as

Influence of ABCB1 polymorphisms and docetaxel pharmacokinetics on pathological response to neoadjuvant chemotherapy in breast cancer patients

  • Pierre Lévy
  • Joseph Gligorov
  • Martine Antoine
  • Keyvan Rezai
  • Eric Lévy
  • Frédéric Selle
  • Pierre Saintigny
  • François Lokiec
  • Danielle Avenin
  • Karine Beerblock
  • Jean-Pierre Lotz
  • Jean-François Bernaudin
  • Anne Fajac
Clinical trial

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.

Keywords

Breast cancer Docetaxel pharmacokinetics and pharmacodynamics ABCB1 Polymorphisms Pharmacogenomics Drug resistance Neoadjuvant Chemotherapy 

Notes

Acknowledgments

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.

Supplementary material

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Supplementary material 1 (PPTX 205 kb)
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Supplementary material 2 (PPTX 235 kb)
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Supplementary material 3 (PPTX 229 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pierre Lévy
    • 1
  • Joseph Gligorov
    • 2
  • Martine Antoine
    • 3
  • Keyvan Rezai
    • 4
  • Eric Lévy
    • 5
  • Frédéric Selle
    • 2
  • Pierre Saintigny
    • 6
  • François Lokiec
    • 4
  • Danielle Avenin
    • 2
  • Karine Beerblock
    • 2
  • Jean-Pierre Lotz
    • 2
  • Jean-François Bernaudin
    • 7
  • Anne Fajac
    • 7
  1. 1.Département de Santé Publique, hôpital Tenon, AP-HP, Inserm UMR S 707Université Pierre et Marie CurieParisFrance
  2. 2.Medical Oncology Department, Francilian Breast intergrouphôpital Tenon, AP-HP, ER2 UPMC Université Pierre et Marie CurieParisFrance
  3. 3.Service d’Anatomo-Pathologie, hôpital Tenon, AP-HPER2 UPMC Université Pierre et Marie CurieParisFrance
  4. 4.Service de PharmacologieCentre René HugueninSt-CloudFrance
  5. 5.Service d’Oncologie, Intergroupe Francilien du seinHEGP, AP-HPParisFrance
  6. 6.Service d’OncologieHôpital Avicenne, AP-HPBobignyFrance
  7. 7.Service d’Histologie-Biologie Tumorale, hôpital Tenon, AP-HPER2 UPMC Université Pierre et Marie CurieParisFrance

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