Breast Cancer Research and Treatment

, Volume 125, Issue 1, pp 145–156 | Cite as

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

  • Gunter von Minckwitz
  • Michael Untch
  • Eveline Nüesch
  • Sibylle Loibl
  • Manfred Kaufmann
  • Sherko Kümmel
  • Peter A. Fasching
  • Wolfgang Eiermann
  • Jens-Uwe Blohmer
  • Serban Dan Costa
  • Keyur Mehta
  • Jörn Hilfrich
  • Christian Jackisch
  • Bernd Gerber
  • Andreas du Bois
  • Jens Huober
  • Claus Hanusch
  • Gottfried Konecny
  • Werner Fett
  • Elmar Stickeler
  • Nadia Harbeck
  • Volkmar Müller
  • Peter Jüni
Clinical trial

Abstract

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

Keywords

Neoadjuvant Breast cancer Pooled analysis Taxanes Anthracyclines trastuzumab 

Notes

Acknowledgments

The pooled analysis was supported by Clinical Trials Unit (CTU) and University of Bern. The conduct of trials was supported by Amgen, Bristol Meyers Squibb, Roche, and Sanofi-Aventis, Germany by providing unrestricted grants and trial medication.

Supplementary material

10549_2010_1228_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Gunter von Minckwitz
    • 1
  • Michael Untch
    • 2
  • Eveline Nüesch
    • 3
  • Sibylle Loibl
    • 1
  • Manfred Kaufmann
    • 4
  • Sherko Kümmel
    • 5
  • Peter A. Fasching
    • 6
  • Wolfgang Eiermann
    • 7
  • Jens-Uwe Blohmer
    • 8
  • Serban Dan Costa
    • 9
  • Keyur Mehta
    • 1
  • Jörn Hilfrich
    • 10
  • Christian Jackisch
    • 11
  • Bernd Gerber
    • 12
  • Andreas du Bois
    • 13
  • Jens Huober
    • 14
  • Claus Hanusch
    • 7
  • Gottfried Konecny
    • 15
  • Werner Fett
    • 16
  • Elmar Stickeler
    • 17
  • Nadia Harbeck
    • 18
  • Volkmar Müller
    • 19
  • Peter Jüni
    • 3
  1. 1.German Breast GroupNeu-IsenburgGermany
  2. 2.Helios-KlinikumBerlin-BuchGermany
  3. 3.Institute of Social and Preventive Medicine and CTU BernUniversity of BernBernSwitzerland
  4. 4.Universitäts-FrauenklinikFrankfurtGermany
  5. 5.Universitäts-FrauenklinikEssenGermany
  6. 6.University Breast Center Franconia, University Hospital ErlangenErlangenGermany
  7. 7.Klinikum zum Roten KreuzMünchenGermany
  8. 8.St. Gertrauden KrankenhausBerlinGermany
  9. 9.Universitäts-FrauenklinikMagdeburgGermany
  10. 10.Henrietten-StiftungHannoverGermany
  11. 11.Städtische KlinikenOffenbachGermany
  12. 12.Universitäts-FrauenklinikRostockGermany
  13. 13.Horst Schmidt KlinikWiesbadenGermany
  14. 14.Universitäts-FrauenklinikTübingenGermany
  15. 15.University of CaliforniaLos AngelesUSA
  16. 16.Hämato-Onkologische PraxisWuppertalGermany
  17. 17.Universitäts-FrauenklinikFreiburgGermany
  18. 18.Brustzentrum, Universitäts-FrauenklinikKölnGermany
  19. 19.Klinik für GynäkologieUniversitätsklinikumHamburgGermany

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