p53 pathway in breast cancer.
In Australia, breast cancer kills around 3000 women annually. Nearly all deaths are a result of acquired resistance to treatment and the development of metastases. Therefore, it is imperative to select the most effective treatment from the outset. The current standard of care for breast cancer is surgery, radiotherapy, and systemic adjuvant therapy (anti-hormone therapy with/without cytotoxic chemotherapy/with or without targeted therapy) to treat the remaining cancer and inhibit recurrence. DNA-damaging agents are frequently used to treat breast cancer, but there is no standardised test for predicting whether the primary regulators of the DNA damage response are active, before treatment is given. Moreover, resistance to targeted therapies is ubiquitous in the clinic. Therefore, there is an urgent need to develop a predictive test in breast cancer that indicates the activity of the pathway being targeted by the therapy. We hypothesise that the development of an assay that comprehensively assesses the tumour suppressor p53 and its regulators will provide critical information that can be used to predict breast cancer recurrence and overall outcome. Hence, this study aimed to define the contribution of aberrations in p53 and its regulators to breast cancer outcomes by targeted re-sequencing. We have re-sequenced p53 and other critical regulators of p53 signalling and the DNA damage response in a cohort of breast cancers by targeted next-generation sequencing.