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Plasma HER2 amplification in cell-free DNA during neoadjuvant chemotherapy in breast cancer

  • Troels BechmannEmail author
  • Rikke Fredslund Andersen
  • Niels Pallisgaard
  • Jonna Skov Madsen
  • Else Maae
  • Erik Hugger Jakobsen
  • Anne Marie Bak Jylling
  • Karina Dahl Steffensen
  • Anders Jakobsen
Original Paper

Abstract

Purpose

Measurement of human epidermal growth factor receptor 2 (HER2) gene amplification in cell-free DNA (cfDNA) is an evolving technique in breast cancer, enabling liquid biopsies and treatment monitoring. The present study investigated the dynamics of plasma HER2 gene copy number and amplification in cfDNA during neoadjuvant chemotherapy.

Patients and methods

The study included 50 patients from a prospective cohort analyzed during neoadjuvant chemotherapy. Fifty healthy women with no history of cancer served as control group and 15 patients with metastatic breast cancer were used to validate the assay. Total cfDNA and HER2 gene amplification were measured by quantitative real-time polymerase chain reaction.

Results

Plasma HER2 gene copy number (p = 0.794), HER2 gene amplification (p = 0.127) and total cfDNA (p = 0.440) did not differ significantly from the levels in the control group. Eighteen patients (36 %) obtained pathological complete response (pCR). HER2 gene copy number before the operation was significantly higher than the baseline level (p < 0.0001), but there was no difference between patients with and without pCR (p = 0.569). Likewise, there was no difference in plasma HER2 gene amplification between tissue HER2-positive and -negative patients (p = 0.754).

Conclusions

The results indicate that neither total cfDNA nor HER2 gene copy number is elevated in primary breast cancer patients compared to healthy controls. The level of both parameters increased during neoadjuvant chemotherapy, but without any relation to treatment effect. There was no indication of plasma HER2 gene amplification in the HER2-positive patients in the neoadjuvant setting.

Keywords

Breast cancer Cell-free DNA HER2 amplification Neoadjuvant chemotherapy 

Notes

Acknowledgments

The study was financed by the Vejle Hospital Research Foundation. The authors thank Marianne Mose Hansen and Lone Frischknecht for their excellent laboratory work and the Department of Surgery, Vejle Hospital, for the enrollment of patients. Furthermore, we would like to thank research assistant Karin Larsen for proofreading.

Conflict of interest

All authors declare no conflicts of interest.

Supplementary material

432_2013_1413_MOESM1_ESM.doc (28 kb)
Supplementary material 1 (DOC 28 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Troels Bechmann
    • 1
    • 2
    Email author
  • Rikke Fredslund Andersen
    • 3
  • Niels Pallisgaard
    • 3
  • Jonna Skov Madsen
    • 1
    • 3
  • Else Maae
    • 2
  • Erik Hugger Jakobsen
    • 2
  • Anne Marie Bak Jylling
    • 4
  • Karina Dahl Steffensen
    • 5
  • Anders Jakobsen
    • 1
    • 2
  1. 1.The Faculty of Health SciencesUniversity of Southern DenmarkOdenseDenmark
  2. 2.Department of OncologyVejle HospitalVejleDenmark
  3. 3.Department of BiochemistryVejle HospitalVejleDenmark
  4. 4.Department of PathologyOdense University HospitalOdenseDenmark
  5. 5.Department of OncologyOdense University HospitalOdenseDenmark

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