Open Access

ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab

  • Authors:
    • Sander Ellegård
    • Cynthia Veenstra
    • Gizeh Pérez‑Tenorio
    • Victor Fagerström
    • Jon Gårsjö
    • Krista Gert
    • Marie Sundquist
    • Annika Malmström
    • Sten Wingren
    • Nils O. Elander
    • Anna‑Lotta Hallbeck
    • Olle Stål
  • View Affiliations

  • Published online on: January 31, 2019     https://doi.org/10.3892/ol.2019.9998
  • Pages: 3371-3381
  • Copyright: © Ellegård et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Trastuzumab has markedly improved the treatment and long‑term prognosis of patients with HER2‑positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2‑associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linköping University Hospital between 2000 and 2007 with trastuzumab for HER2‑positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high‑grade ERBB2 (HER2) amplification level of ≥6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2‑0.9] and progression‑free survival (HR=0.3; 95% CI: 0.1‑0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High‑grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (≥3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0‑4.0) and shorter progression‑free survival (HR=2.1; 95% CI: 1.0‑4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab‑treated HER2‑positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.
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March-2019
Volume 17 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Ellegård S, Veenstra C, Pérez‑Tenorio G, Fagerström V, Gårsjö J, Gert K, Sundquist M, Malmström A, Wingren S, Elander NO, Elander NO, et al: ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab. Oncol Lett 17: 3371-3381, 2019
APA
Ellegård, S., Veenstra, C., Pérez‑Tenorio, G., Fagerström, V., Gårsjö, J., Gert, K. ... Stål, O. (2019). ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab. Oncology Letters, 17, 3371-3381. https://doi.org/10.3892/ol.2019.9998
MLA
Ellegård, S., Veenstra, C., Pérez‑Tenorio, G., Fagerström, V., Gårsjö, J., Gert, K., Sundquist, M., Malmström, A., Wingren, S., Elander, N. O., Hallbeck, A., Stål, O."ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab". Oncology Letters 17.3 (2019): 3371-3381.
Chicago
Ellegård, S., Veenstra, C., Pérez‑Tenorio, G., Fagerström, V., Gårsjö, J., Gert, K., Sundquist, M., Malmström, A., Wingren, S., Elander, N. O., Hallbeck, A., Stål, O."ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab". Oncology Letters 17, no. 3 (2019): 3371-3381. https://doi.org/10.3892/ol.2019.9998