Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

4247 - Changes in ER pathway activity score during neoadjuvant letrozole to assess therapy response and predict disease free survival (DFS) in ER positive breast cancer patients


29 Sep 2019


Poster Display session 2


Tumour Site

Breast Cancer


Arran Turnbull


Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240


A.K. Turnbull1, M. A. Inda2, A. van de Stolpe3, D. Keizer4, D. Clout5, H. van Zon5, M. Akse4, A. Fernando6, C. Martinez-Perez1, J..M. Dixon7, A.H. Sims1

Author affiliations

  • 1 Mrc Institute Of Genetics And Molecular Medicine, University of Edinburgh, EH4 2XU - Edinburgh/GB
  • 2 Precision Diagnostics, Philips Research, 5656AE - Eindhoven/NL
  • 3 Precision Diagnostics, Philips Research, 5656 AE - Eindhoven/NL
  • 4 Molecular Pathway Diagnositics, Philips, Eindhoven/NL
  • 5 Precision Diagnostics, Philips Research, 5656 AE Eindhoven - Eindhoven/NL
  • 6 Mrc Institute Of Genetics And Molecular Medicine, University of Edinburgh, Edinburgh/GB
  • 7 Edinburgh Breast Unit, Western General Hospital, EH4 2XU - Edinburgh/GB


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 4247


Despite ER positive IHC staining, some patients do not respond to neoadjuvant endocrine therapy, suggesting that ER staining lacks specificity to predict response. We developed a method to infer a quantitative signal transduction pathway activity score (PAS) from mRNA levels (microarray, qPCR) of pathway-associated transcription factor target genes. Initial studies suggest that ER PAS may have higher specificity than ER IHC in predicting endocrine therapy response. In this study, we correlated pre-treatment ER PAS and changes in ER PAS during neoadjuvant letrozole treatment to therapy response and DFS.


We collected fresh frozen RNA from tumor samples of 30 ER IHC positive post-menopausal patients with primary localized breast cancer, treated with neoadjuvant letrozole at Edinburgh Western General. In total, 30 pre, 25 mid (median 27 days), and 29 post-treatment (median 136 days) samples were analysed. Clinical outcome was assessed (RECIST, n = 29) at circa 3 months treatment by 3D ultrasound, with 1 complete (CR), 21 partial responses (PR), 2 stable (SD), and 5 progressive diseases (PD). Using RT-qPCR, target gene expression was measured for ER, androgen receptor, PI3K, Hedgehog, TGFβ and Wnt pathways. PAS were expressed on a normalized scale (0 to 100).


Pre-treatment ER PAS was significantly higher in responders (CR/PR) than non-responders (SD/PD), PAS=45 vs 24, respectively, T-test p = 0.01. Pre-treatment ER PAS correlated with decrease in ER PAS during treatment (cor=0.87 and 0.7, mid and-post treatment, respectively). At mid-treatment, ER PAS of responders had decreased to PAS of non-responders (20 vs 19, respectively), remaining low during further treatment. Decrease in ER PAS was significantly higher in responders (-30) than non-responders (-6), p = 0.01. Higher ER PAS after treatment correlated to shorter DFS (COX proportional hazards p = 0.02). Baseline PAS of other pathways did not correlate with response, but changed significantly during treatment.


This study confirms that ER PAS in ER-positive patients, measured before and after neoadjuvant endocrine therapy, has potential to predict and assess therapy response, and predict DFS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Philips Electronics Nederland B.V., acting through its HealthWorks Molecular Pathway Dx.


Has not received any funding.


M. A. Inda: Full / Part-time employment: Philips Reseach. A. van de Stolpe: Full / Part-time employment, has Philips stocks: Philips Research. D. Keizer: Full / Part-time employment: Philips. D. Clout: Full / Part-time employment: Philips Reasearch. H. van Zon: Full / Part-time employment: Philips Reasearch. M. Akse: Full / Part-time employment: Philips. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.