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Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer—results from the GeparQuattro study (GBG 40)

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Abstract

Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline–taxane–trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana™ automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2–0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.

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Acknowledgments

We would like to thank Britta Bayer for her excellent technical assistance.

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Authors and Affiliations

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

    Gunter von Minckwitz & Sibylle Loibl

  2. Department of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany

    Silvia Darb-Esfahani & Carsten Denkert

  3. Breast Center, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Jens Huober

  4. Bethanien Krankenhaus, Frankfurt, Germany

    Hans Tesch

  5. Universitäts-Frauenklinik, Frankfurt, Germany

    Christine Solbach

  6. St. Barbara Kliniken Heessen, Hamm, Germany

    Frank Holms & Katharina Tiemann

  7. Universitätsklinikum Schleswig-Holstein, Campus Kiel, Frauenklinik, Kiel, Germany

    Holger Eidtmann

  8. Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Frauenklinik, Lübeck, Germany

    Klaus Dietrich

  9. Onkologische Schwerpunktpraxis, Bielefeld, Germany

    Marianne Just

  10. Mutterhaus Der Borromäerinnen, Trier, Germany

    Michael R. Clemens

  11. Rotkreuzklinikum, Munich, Germany

    Claus Hanusch

  12. Henriettenstiftung, Hannover, Germany

    Iris Schrader

  13. Johanniter-Krankenhaus, Genthin-Stendal, Stendal, Germany

    Stephan Henschen & Kurt Diebold

  14. St. Josefs Hospital, Wiesbaden, Germany

    Gerald Hoffmann

  15. Helios-Klinikum Berlin-Buch, Berlin, Germany

    Michael Untch

Authors
  1. Gunter von Minckwitz
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  2. Silvia Darb-Esfahani
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  3. Sibylle Loibl
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  4. Jens Huober
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  5. Hans Tesch
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  6. Christine Solbach
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  7. Frank Holms
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  8. Holger Eidtmann
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  9. Klaus Dietrich
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  10. Marianne Just
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  11. Michael R. Clemens
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  12. Claus Hanusch
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  13. Iris Schrader
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  14. Stephan Henschen
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  15. Gerald Hoffmann
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  16. Katharina Tiemann
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  17. Kurt Diebold
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  18. Michael Untch
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  19. Carsten Denkert
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Corresponding author

Correspondence to Gunter von Minckwitz.

Additional information

This study is conducted for the German Breast Group and the AGO Breast Group.

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von Minckwitz, G., Darb-Esfahani, S., Loibl, S. et al. Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer—results from the GeparQuattro study (GBG 40). Breast Cancer Res Treat 132, 863–870 (2012). https://doi.org/10.1007/s10549-011-1621-0

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  • DOI: https://doi.org/10.1007/s10549-011-1621-0

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