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

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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.

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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.

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Authors and Affiliations

  1. German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Str. 12, 63263, Neu-Isenburg, Germany

    Gunter von Minckwitz, Sibylle Loibl & Keyur Mehta

  2. Helios-Klinikum, Berlin-Buch, Germany

    Michael Untch

  3. Institute of Social and Preventive Medicine and CTU Bern, University of Bern, Bern, Switzerland

    Eveline Nüesch & Peter Jüni

  4. Universitäts-Frauenklinik, Frankfurt, Germany

    Manfred Kaufmann

  5. Universitäts-Frauenklinik, Essen, Germany

    Sherko Kümmel

  6. University Breast Center Franconia, University Hospital Erlangen, Erlangen, Germany

    Peter A. Fasching

  7. Klinikum zum Roten Kreuz, München, Germany

    Wolfgang Eiermann & Claus Hanusch

  8. St. Gertrauden Krankenhaus, Berlin, Germany

    Jens-Uwe Blohmer

  9. Universitäts-Frauenklinik, Magdeburg, Germany

    Serban Dan Costa

  10. Henrietten-Stiftung, Hannover, Germany

    Jörn Hilfrich

  11. Städtische Kliniken, Offenbach, Germany

    Christian Jackisch

  12. Universitäts-Frauenklinik, Rostock, Germany

    Bernd Gerber

  13. Horst Schmidt Klinik, Wiesbaden, Germany

    Andreas du Bois

  14. Universitäts-Frauenklinik, Tübingen, Germany

    Jens Huober

  15. University of California, Los Angeles, USA

    Gottfried Konecny

  16. Hämato-Onkologische Praxis, Wuppertal, Germany

    Werner Fett

  17. Universitäts-Frauenklinik, Freiburg, Germany

    Elmar Stickeler

  18. Brustzentrum, Universitäts-Frauenklinik, Köln, Germany

    Nadia Harbeck

  19. Klinik für Gynäkologie, Universitätsklinikum, Hamburg, Germany

    Volkmar Müller

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  1. Gunter von Minckwitz
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  2. Michael Untch
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  3. Eveline Nüesch
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  14. Bernd Gerber
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  15. Andreas du Bois
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  16. Jens Huober
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  20. Elmar Stickeler
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  21. Nadia Harbeck
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  22. Volkmar Müller
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  23. Peter Jüni
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Corresponding author

Correspondence to Gunter von Minckwitz.

Additional information

This study is conducted on behalf of the German Breast Group and AGO-B study group.

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von Minckwitz, G., Untch, M., Nüesch, E. et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125, 145–156 (2011). https://doi.org/10.1007/s10549-010-1228-x

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  • DOI: https://doi.org/10.1007/s10549-010-1228-x

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