Breast Cancer Research and Treatment

, Volume 125, Issue 2, pp 505–510

Potent CYP2D6 Inhibiting drugs do not increase relapse rate in early breast cancer patients treated with adjuvant tamoxifen

Authors

  • Nava Siegelmann-Danieli
    • Department of Specialized MedicineMaccabi Healthcare Services
  • Daniel Kurnik
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
    • Sackler School of MedicineTel Aviv University
  • Yossi Lomnicky
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
  • Janet Vesterman-Landes
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
  • Itzhak Katzir
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
  • Martin Bialik
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
    • Department of Pharmaceutics and Clinical PharmacologyMaccabi Healthcare Services
    • Sackler School of MedicineTel Aviv University
Epidemiology

DOI: 10.1007/s10549-010-1008-7

Cite this article as:
Siegelmann-Danieli, N., Kurnik, D., Lomnicky, Y. et al. Breast Cancer Res Treat (2011) 125: 505. doi:10.1007/s10549-010-1008-7

Abstract

Endoxifen, the most active metabolite of the prodrug tamoxifen, is produced by cytochrome P450 CYP2D6. Breast cancer patients treated with tamoxifen who have reduced CYP2D6 activity, related to either genetic variation or drug inhibition, may have inferior outcomes. To assess the effect of concomitant CYP2D6 inhibiting drug use on clinical outcomes of breast cancer patients treated with adjuvant tamoxifen. We conducted a retrospective database analysis. Women with non-metastatic estrogen receptor positive tumors who had completed adjuvant tamoxifen therapy for 2 years, without treatment with adjuvant aromatase inhibitors or early relapse, were included. Patients were classified as users of CYP2D6 inhibitors if they purchased strong CYP2D6 inhibiting drugs for ≥4 consecutive months during tamoxifen treatment. Tumors were classified as “high risk” if adjuvant chemotherapy was prescribed. Primary endpoint was disease free (DFS) and secondary endpoint was overall survival (OS). 902 patients treated with tamoxifen (median duration, 4.9 years) were followed for a median period of 5.9 years. Fifty-nine (6.5%) patients were users of CYP2D6 inhibitors (median duration, 23 months). DFS at 3 years (corresponding to 5 years after tamoxifen initiation) did not differ between users and non-users of CYP2D6 inhibiting drugs (92.7 vs. 93.0%, respectively; adjusted P = 0.44). OS at 3 years was lower in the patients using CYP2D6 inhibiting drugs: 89.4 vs. 93.8%, but after adjustment for age and comorbidities this difference was not significant (P = 0.20). Overall recurrence rates did not differ between users and non-users of CYP2D6 inhibiting drugs (11.8 vs. 19.0% respectively, P = 0.23). Concomitant prolonged therapy with strong CYP2D6 inhibiting drugs does not affect adversely DFS and recurrence rates in tamoxifen-treated early breast cancer patients.

Keywords

TamoxifenCYP2D6 inhibitionDisease-free survivalOverall survivalDrug interaction

Copyright information

© Springer Science+Business Media, LLC. 2010