Stopping breast cancer before it starts: Targeting the earliest changes that drive cancer in people with BRCA1 mutations

Dr Thierry Jardé is a Laboratory Head in the Department of Anatomy and Developmental Biology at Monash University. He is the Director of the Monash Biomedicine Discovery Institute organoid program.

The challenge:

Women who carry a faulty BRCA1 gene have a much higher lifetime risk (around 72%) of developing breast cancer than the general population. Among those who develop cancer, most are diagnosed with Triple Negative Breast Cancer (TNBC), an aggressive subtype that can be difficult to treat.

The BRCA1 gene plays an essential role in repairing DNA damage and keeping cells healthy. When the BRCA1 gene is not functioning properly due to a genetic mutation, cells accumulate genetic errors that increase the risk of cancer. Research suggests that a BRCA1 gene mutation does more than just cause early abnormal changes in breast cells. It also changes the surrounding breast tissue, creating conditions that make it easier for cancer to develop and grow. However, the exact nature of these changes in the local tissue environment remains unclear.

Current prevention options for people with BRCA1 mutations are limited and often involve major surgery, highlighting the need for new, less invasive approaches.

Project description:

Dr Thierry Jardé’s Pink Sky Grant project, funded by the National Breast Cancer Foundation (NBCF), aims to identify the earliest changes in breast tissue that lead to cancer in women with a BRCA1 mutation. Using advanced technologies, he and his team, including Dr Dilys Leung, Professor Gary Richardson, Professor Delphine Merino and Dr Shanika Amarasinghe, at Monash University will study breast tissue from women with BRCA1 mutations at different stages: those without cancer, those that have abnormal, precancerous cells, and those with early breast cancer.

The researchers will examine how breast cells and surrounding support cells, such as fibroblasts, behave, communicate and change when BRCA1 is not working properly. These interactions are thought to play a key role in creating conditions that enable cancer to develop.

This data will then be used to build advanced laboratory models using gene editing technology. These models will closely mimic BRCA1 mutations in breast tissue, allowing the team to map the step-by-step chain of events that leads from healthy tissue to early breast cancer development.

By identifying the key signals and pathways that drive the earliest changes that lead to breast cancer, this research could support new strategies to detect, delay or prevent cancer development in people with BRCA1 mutations.

Potential impact:

If successful, Dr Jardé’s Pink Sky Grant project could transform how breast cancer is prevented and detected in people with BRCA1 mutations. This approach may lead to less invasive prevention options, new tools for early detection, and more personalised monitoring for people at high genetic risk. Beyond BRCA1-related breast cancer, the knowledge gained could also improve understanding of how other breast cancers begin and develop.

Grant code: 2025/PS0149
Active years: 2026-2029
Scientific project title: Stop it before it starts: targeting tumour cell-fibroblast communication to prevent breast tumour initiation