PreBRCATx · Understanding Precancerous changes in BReast CAncer for the development of Therapeutic interceptions

In this programme, we will leverage our understanding of the cellular and molecular changes that precede cancer in high-risk individuals to intercept and prevent the development of the disease. Despite significant advances in immune and targeted therapies, the molecular and cellular complexity of late-stage tumours continues to pose a major barrier to developing a definitive “cancer cure”. This underscores the urgency of identifying those at risk and intervening prophylactically to prevent tumour development. Early detection and interception can significantly enhance the long-term survival of patients. Over the past decade, we have utilised a combination of single-cell genomics, mouse models, and primary human samples to map cellular changes in the breast during homeostasis and tumour initiation. Building on this expertise, we aim to deepen our understanding of precancerous changes driven by BRCA1, BRCA2, and PALB2 mutations, test the efficacy of approved and nearly approved drugs, and develop and test a preventative vaccine in pre-clinical models for these mutations. The PreBRCATx integrated approach is designed to deliver significant impacts for individuals at high risk of breast cancer and, if successful, could serve as a model for other types of hereditary cancers in the future. We aim to gather sufficient evidence to initiate clinical prevention trials, focusing on women with pathological variants of BRCA1, BRCA2, and PALB2 and we anticipate setting up a window of opportunity trial by the end of the programme. The programme will also generate new tools, resources, and data, empowering others in the breast cancer field and benefiting researchers of other solid cancers. Early detection and prevention of cancer could significantly mitigate the socioeconomic impact of late-stage cancer diagnoses and treatments, aligning with the ambitions of policymakers and healthcare providers across Europe to promote a healthier and longer life.