Grant: Project Grant

Despite a decline in the number of breast-cancer related deaths in recent years, the overall incidence is increasing. Breast cancer progresses through different stages, and modern techniques can identify pre-cancerous lesions. One problem is that not all lesions will progress to breast cancer, but clinicians are unable to predict which are at the highest risk of progressing to cancer. Although detection methods have improved to the point where breast lesions can be detected at the earliest stages, clinicians are currently unable to predict which of these lesions will progress to invasive cancer. We hypothesized that a deeper understanding of the mechanisms underlying pre-invasive breast cancer progression would enable us to identify changes that are associated with progression to cancer. We identified a protein called Par6, which is frequently up-regulated in advanced breast cancers. We found that Par6 was expressed in different regions of cancer cells, and where Par6 was located correlated with different grades - an indicator of how quickly a tumour can grow and spread. Importantly, we could identify these changes in some of the earliest pre-cancer lesions. We hypothesize that Par6 may be a marker to help predict lesions that have the highest likelihood of progressing to cancer. In this project we have four aims to test this hypothesis. 1) We will examine a large number of samples from breast cancer biopsies and determine if changes in Par6 correlate with patient outcomes; 2) We will identify whether different Par6 expression patterns correlate with different signaling pathways that could contribute to cancer progression; 3) Determine the consequence of different Par6 expression patterns on breast cancer progression using novel mouse models.