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ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.ORCID-id: 0000-0002-3084-7881
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Department of Surgery, Kalmar Hospital, Kalmar.
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2019 (engelsk)Inngår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 17, nr 3, s. 3371-3381Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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, Linkoping 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 amp;gt;= 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 (amp;gt;= 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.

sted, utgiver, år, opplag, sider
Athens, Greece: Spandidos Publications , 2019. Vol. 17, nr 3, s. 3371-3381
Emneord [en]
HER2; brain metastasis; protein tyrosine phosphatase non-receptor type 2; ribosomal protein S6 kinase B1; PI3K; phosphatase and tensin homolog
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Identifikatorer
URN: urn:nbn:se:liu:diva-155540DOI: 10.3892/ol.2019.9998ISI: 000460555900098PubMedID: 30867772Scopus ID: 2-s2.0-85062153648OAI: oai:DiVA.org:liu-155540DiVA, id: diva2:1297711
Merknad

Funding Agencies|Swedish Cancer Society [17-0479]; Medical Research Council of Southeast Sweden [FORSS-757671]; ALF Grants Region Ostergotland [LIO-795201]; Stiftelsen Onkologiska Klinikernas Forskningsfond i Linkoping [2016-06-21]

Tilgjengelig fra: 2019-03-20 Laget: 2019-03-20 Sist oppdatert: 2019-08-27bibliografisk kontrollert

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