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Breast Cancer Research and Treatment

, Volume 147, Issue 1, pp 61–68 | Cite as

Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial

  • Volkmar Müller
  • Stephan Gade
  • Bettina Steinbach
  • Sibylle Loibl
  • Gunter von Minckwitz
  • Michael Untch
  • Kathrin Schwedler
  • Kristina Lübbe
  • Christian Schem
  • Peter A. Fasching
  • Christine Mau
  • Klaus Pantel
  • Heidi Schwarzenbach
Preclinical study

Abstract

Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.

Keywords

Cell-free microRNAs Lapatinib therapy Trastuzumab therapy 

Notes

Acknowledgments

This study was supported by the Deutsche Krebshilfe e.V (199232) and ERC (European Research Council) Advanced Investigator Grant (ERC-2010 AsG 20100317 DISSECT).

Conflict of interest

No potential conflicts of interest were disclosed by all authors.

Supplementary material

10549_2014_3079_MOESM1_ESM.ppt (102 kb)
Fig. S1 Diagram showing the number of participants in the GeparQuinto study with HER2 positive tumors analyzed (PPT 102 kb)
10549_2014_3079_MOESM2_ESM.pptx (79 kb)
Fig. S2 Comparison of the three miRs between trastuzumab and lapatinib before and after therapy. All p-values were calculated using two-sided Wilcoxon tests (PPTX 79 kb)
10549_2014_3079_MOESM3_ESM.docx (15 kb)
Table S1 (DOCX 15 kb)
10549_2014_3079_MOESM4_ESM.docx (18 kb)
Table S2 (DOCX 18 kb)
10549_2014_3079_MOESM5_ESM.docx (18 kb)
Table S3 (DOCX 18 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Volkmar Müller
    • 1
  • Stephan Gade
    • 3
  • Bettina Steinbach
    • 2
  • Sibylle Loibl
    • 4
  • Gunter von Minckwitz
    • 4
  • Michael Untch
    • 4
  • Kathrin Schwedler
    • 5
  • Kristina Lübbe
    • 6
  • Christian Schem
    • 7
  • Peter A. Fasching
    • 8
  • Christine Mau
    • 4
  • Klaus Pantel
    • 2
  • Heidi Schwarzenbach
    • 2
  1. 1.Clinic of GynecologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of Tumor BiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Germany German Breast GroupNeu-IsenburgGermany
  4. 4.Interdisciplinary Breast Cancer CenterHELIOS Klinikum Berlin-BuchBerlinGermany
  5. 5.Department of Gynecology and ObstetricsUniversity Hospital FrankfurtFrankfurtGermany
  6. 6.Department of GynecologyHenrietten Stiftung HannoverHannoverGermany
  7. 7.Department of Obstetrics and GynecologyUniversity KielKielGermany
  8. 8.Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMNUniversity Hospital ErlangenHamburgGermany

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