Project 462956

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with more deaths occurring within the first 5 years after diagnosis than for other subtypes. Breast cancers are routinely tested for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). TNBC is defined by lack of these three receptors. Significant progress has been made towards targeted treatment of Luminal (ER-receptor positive), and HER2 subtypes of breast cancers. Although TNBCs account for approximately 15% of breast cancer diagnosis because of their aggressive biology they account for approximately 25% of breast cancer-related deaths. To understand why some TNBCs behave more aggressively we have developed advanced molecular methods to look at genomic changes in tumour cells and infiltrating immune cells. We have recent evidence that the variability of these cells is related to metastasis. The methods we have developed can be used to study a group of samples that have been stored for more than 10 years. In this group we know which tumours were the most aggressive and killed the patients. We will study tumour that has spread beyond the breast to lymph nodes. We will also identify molecular alterations present in TNBCs that did not respond to chemotherapy. Our studies will lead to a better understanding of the molecular alterations involved in the progression of TNBC, and some of the features that are associated with the shortest survival. It would be very helpful to be able to identify the women with the worst prognosis TNBCs and then they could be targeted for more intensive therapy. Conversely, treatment could be reduced in women found to have less aggressive forms of TNBC which would reduce both side effects and costs. Ultimately, we believe this work will result in promising new therapeutic targets.