The inherent inter and intra-heterogeneity of breast cancer is one of the major bottlenecks to improved therapeutic response and overall survival rates. Comprehensive tissue banks are required not only for biochemical, molecular, and genomic studies, but for the creation of the renewable patient derived xenograft (PDX) and matching primary cell lines for further in vivo and in vitro studies.
It is widely accepted that PDXs represent superior preclinical modelling tools. Not only do PDX models maintain genomic, transcriptomic, proteomic and histopathological features, but PDXs have also been shown to mimic the therapeutic response and metastatic phenotype of the originating patient tumour (1).
Our aim is to create a nationally available bioresource of 50+ viably frozen primary and metastatic breast cancer PDX models. The PDX, along with the matching patient tumour and normal tissues, will be characterized and in-depth clinical data will be collected on each case. We have employed a multi-disciplinary approach across multiple Australian centres to achieve the most comprehensive set of breast cancer samples. To date, 36 lesions of varied subtypes have been xenografted, and eight PDX models have been successfully established.
However, the majority of breast cancer related deaths is due to metastatic disease. Metastatic lesions are not readily available to researchers, due to the difficult nature of collecting samples and the lack of biopsy and surgical intervention of these lesions. We have established a rapid autopsy program in order to collect metastatic lesions from pre-consented patients; currently one has been conducted, successfully collecting 13 metastatic lesions. This will allow local and international researchers to study the metastatic progenies of breast cancer and identify the underlying genomic, transcriptomic and proteomic drivers of the metastatic disease.