125P - Components of the PI3K/Akt pathway as prognostic factors in metastatic HER2-positive breast cancer treated with trastuzumab

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Biomarkers
Breast Cancer, Metastatic
Presenter Cynthia Veenstra
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors C. Veenstra1, S. Ellegård1, G. Pérez-Tenorio1, V. Fagerström1, J. Gårsjö1, K. Briedis1, M. Sundqvist2, A. Malmström1, S. Wingren3, O. Stål1
  • 1Clinical And Experimental Medicine And Department Of Oncology, University Hospital Linköping, 581 85 - Linköping/SE
  • 2Surgery, County Hospital, 39126 - Kalmar/SE
  • 3Medicine And Health, Universitetssjukhuset Orebro, 701 82 - Orebro/SE

Abstract

Background

HER2-positive breast cancer is an aggressive form of breast cancer, for which trastuzumab has been successfully used as treatment to improve patient outcome. Unfortunately, trastuzumab resistance often occurs, causing a major clinical challenge and to date no reliable biomarkers predicting resistance are available. We aimed to explore prognostic values of factors in the PI3K/Akt pathway.

Methods

A clinical cohort of 47 patients with metastatic HER2-positive breast cancer was used. All patients received trastuzumab as part of their palliative treatment. Copy number variations and protein expressions of several components in the PI3K/Akt pathway were determined using droplet digital PCR and immunohistochemistry, respectively.

Results

Patients with tumours showing high-grade ERBB2 amplification had a better overall survival (OS) and progression-free survival (PFS) compared with those with low-grade amplification. One through two copies of the gene encoding the tyrosine phosphatase PTPN2 resulted in a significantly improved OS and a trend towards better PFS. Similar results, albeit non-significant, were found with PTPN2 protein levels. Patients with cytoplasmic Met expression showed a trend towards better PFS than patients without this expression and high cytoplasmic S6K1 expression was related to a longer OS.

Conclusions

The present results suggest that high-grade ERBB2 amplification and 0-2 copies of PTPN2 are positive prognostic factors in metastatic HER2-positive breast cancer treated with trastuzumab. This, together with the indicative findings on Met and S6K1, suggests that trastuzumab is more effective in highly proliferative tumours.

Clinical trial indentification

Legal entity responsible for the study

Olle Stål

Funding

Swedish Cancer Society, Medical Research Council of Southeast Sweden, Onkologiska klinikernas forskningsfond Linköping

Disclosure

All authors have declared no conflicts of interest.