23O - Clinical patterns of metastatic spread from formalin-fixed, paraffin-embedded (FFPE) expression profiles: A case-control study of 1,357 breast cance...

Date 07 May 2015
Event IMPAKT 2015
Session Best abstracts session
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Katherine Lawler
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors K. Lawler1, E. Papouli2, A. Tutt3, T. Ng4, S. Pinder1, P. Parker1, L. Holmberg5, C. Gillett1, A. Grigoriadis3, A. Purushotham1
  • 1Division Of Cancer Studies, King's College London, London/UK
  • 2Nihr Comprehensive Biomedical Research Centre At Guy's And St Thomas' Nhs Foundation Trust, King's College London, London/UK
  • 3Breakthrough Breast Cancer Research Unit, King's College London Guy's Hospital, SE1 9RT - London/UK
  • 4Richard Dimbleby Department Of Cancer Research, Randall Division Of Cell And Molecular Biophysics, King's College London, London/UK
  • 5Cancer Epidemiology Unit, King's College London, London/UK

Abstract

Body

Metastases are the main cause of breast cancer mortality and prediction of distant metastatic sites is limited. To discover prognostic associations with patterns of bone and/or visceral metastatic spread observed in a clinical setting, we performed a whole genome expression study on a cohort of FFPE samples from 1,357 patients with comprehensive long-term follow-up. An efficient case-control design was used to include four distinct patterns of metastatic spread: first metastasis to bone and viscera within a six month period; predilection to bone, with delayed or no visceral metastasis; predilection to viscera; and no metastasis. A control series with a typical breast cancer subtype distribution was included for efficient estimation of prognostic utility in a clinical population. High quality RNA of 953 samples was analysed with the Illumina WG-DASL expression array, and stringent post-processing provided robust datasets for 683 primary tumours and 79 lymph node metastases (LNM). Expression profiles were generally conserved in patient-matched LNM, in which RNA quality was overall superior to primary tumour samples. Gene expression programs including proliferation, cell motility, presence of stem-cell-like cells and immune/lymphocytic infiltration varied across metastatic groups. Specific expression profiles were discovered which implicated distinct components of the tumour microenvironment and mechanisms of cell proliferation in bone and/or visceral metastatic spread. Multivariable competing risk analyses indicated these expression profiles may have specific prognostic utility in a clinical population. This study revealed clinically relevant patterns of metastatic spread (to bone and/or viscera) associated with specific gene expression profiles, and extends substantially our understanding of the suitability of long-term stored FFPE samples, currently an under-utilised resource for studying the biology of long-term metastatic progression with potential applications for targeted clinical trials.

The authors acknowledge C Naceur-Lombardelli1, A Mera5, O Agbaje5, D Rhodes1 and A.C.C. Coolen for contributions to this work.

Disclosure: All authors have declared no conflicts of interest.