Oral Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

The development of personalised diagnostic tests and therapeutic strategies in breast cancer (#103)

Jamie R Kutasovic 1 , Esdy Rozali 1 , Mariska Miranda 1 , Sunil R Lakhani 2 3 , Fares Al-Ejeh 1
  1. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. University of Queensland, Herston, QLD, Australia
  3. Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia

Despite some improvement in the overall survival rates of breast cancer, it remains the second most common cause of cancer related deaths in Australia. Currently we are unable to accurately predict patients’ response to therapies and their long-term outcome. We developed and patented a gene signature that can predict which patients suffer from aggressive disease and succumb to their disease within 5 years of diagnosis. This test, the integrated Breast Cancer Recurrence score (iBCR), can also predict which emerging targeted therapies should be added to standard treatments to improve outcomes. In addition, 21 of the genes in this signature are novel potential drug targets that have not previously been described in aggressive breast tumours.

We have confirmed the prognostic power of the iBCR, irrespective of clinicopathological features, in a pilot study using the NanoString nCounter Dx platform by measuring the expression of the top 125 genes within the signature in a cohort of 48 patients from the Queensland Follow Up (QFU) cohort with 25 years of follow up (p<0.0001). Future work will expand this test to the full 275-gene set across 500 patients from the QFU cohort. In vitro siRNA screening of the 21 novel genes revealed that at least 10 of these genes are required for breast cancer cell survival. We have started validation of the top 4 hits and these studies confirm the requirement of these genes in breast cancer progression. These data will pave the way towards the study of these genes as new drug targets. Collectively, our test addresses the significant issue of heterogeneous responses to breast cancer treatment. The iBCR platform aims to improve both patients' clinical outcome and quality of life by directing more appropriate treatment with greater likelihood of success, and preventing overtreatment for those with a less aggressive tumor type.