Poster Presentation 29th Lorne Cancer Conference 2017

Development of a national bioresource of patient derived xenografts (PDX) of primary and metastatic breast cancer, for the improvement of preclinical modeling and biomarker discovery (#167)

Kate Harvey 1 2 , Lisa Devereux 3 , Caroline L Cooper 4 5 , Anne Holliday 1 , Hugh Carmalt 6 7 8 , Cindy Mak 9 , Sanjay Warrier 7 9 10 11 , Laurence Gluch 6 7 8 , Belinda Chan 9 , April Wong 9 , Christina Selinger 2 , Jane M Beith 7 12 , Sandra A O'Toole 1 2 7 10 , Robin Anderson 3 13 , Alexander Swarbrick 1 10
  1. The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  3. Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. Pathology Queensland, Herston, QLD, Australia
  5. School of Medicine, University of Queensland, Herston, QLD, Australia
  6. Department of Breast and Endocrine Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
  7. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  8. The Strathfield Breast Centre, Strathfield, NSW, Australia
  9. Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  10. St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW, Australia
  11. Department of Breast Surgery, Prince of Wales Hospital, Randwick, NSW, Australia
  12. Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
  13. Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia

The complex heterogeneity of breast cancer continues to be one of the largest hurdles to the improvement of therapeutic response and overall survival rates. Recently, research has aimed to better understand and mechanistically characterise the nature of metastatic disease, which remains the major cause of breast cancer related deaths. Unfortunately, residual disease remains very challenging to model and metastatic lesions are rarely available to researchers. More comprehensive resources, including renewable Patient Derived Xenograft (PDX) banks, are needed to adequately represent primary and metastatic disease. This will allow in vivo and in vitro modelling of disease and offer a unique opportunity to develop therapeutic strategies for the suppression of metastatic lesions.

Multi-centered funding was obtained to create a nationally available bioresource of viably frozen primary and metastatic breast cancer PDX models. The program uses a multi-disciplinary approach to ensure the most comprehensive set of breast cancer samples from various subtypes are collected and analysed. To date, over 80 primary and 70 metastatic lesions have been xenografted, with over 25 primary and numerous metastatic models successfully implanting into immunocompromised mice. Intense characterisation of these models is currently being conducted.

Moreover, funding provided by the National Breast Cancer Foundation (NBCF) has allowed a new Rapid Autopsy program named BROCADE (BReast Origin CAncer tissue DonatEd after death) to be established. This multi-institutional program collects metastatic lesions from consented patients who die of metastatic breast cancer (Peter MacCallum Cancer Centre and Royal Brisbane and Womans Hospital/University of Queensland). To date, five autopsies have been conducted, collecting numerous metastatic lesions from diverse organs (bone, liver, lung, brain etc.) for standard tissue biobanking, as well as xenografting and single-cell dissociation and transcriptomic analysis at the Garvan Institute of Medical Research. Additional national sites will commence recruitment in the coming year. BROCADE has been established as an open-access infrastructure resource subject to appropriate ethical approvals and scientific review and will allow researchers to identify underlying genomic, transcriptomic and proteomic drivers of primary and metastatic disease, and ultimately understand the metastatic progression of breast cancer.