Unlocking new treatment paths for people carrying a BRCA1 gene mutations

The challenge:

People who inherit a BRCA1 gene mutation have a high life-time risk of breast cancer of around 70%. They are commonly diagnosed at a younger age, with cancers that tend to grow quickly and may return after initial treatment.

Many BRCA1-related breast cancer diagnoses are Triple Negative Breast Cancer (TNBC), which has fewer treatment options as these tumours lack the common hormone and protein targets used in the treatment of other types of breast cancer. Currently, there are few preventive options besides mastectomy (removal of breast tissue) available to women with BRCA1 mutations.

Project description:

In this NBCF-funded project, Professor Jane Visvader and her team at WEHI aim to improve outcomes for people with inherited BRCA1 mutations by developing a greater understanding of the earliest changes that occur inside breast tissue of BRCA1 mutation carriers before cancer forms, how cancer cells and surrounding immune cells interact, and which pathways in mutated BRCA1 cells are involved in the development of early and advanced tumours. Their findings could eventually lead to the discovery of earlier ‘warning signs’ of breast cancer that may enable the development of prevention strategies and new targeted treatments.

Professor Visvader’s project uses advanced genomic technologies to study and map thousands of individual breast and immune cells in fine detail. This will enable them to understand the behaviour of single cells before they become cancerous and assist in pinpointing the genes and pathways that fuel BRCA1-related breast cancers like TNBC.

The team have developed powerful laboratory models, including models using patient-derived tumour samples with BRCA1 gene mutations, to mimic how the disease behaves in humans. They will follow mutated BRCA1 cells as they progress from precancerous stages to fully developed tumours using cell barcoding, which labels cells with unique tags so their ‘family trees’ can be traced over time, and single-cell RNA sequencing, which reveals which genes are active in each cell. In addition, they will study immune cells in surrounding tissue, which could help them identify ways to overcome the suppression of the immune system against TNBC cells.

The team will also test a new combination therapy to block RANK, a protein that is found in high levels in BRCA1-related tumours and linked to tumour growth.

Potential impact:

In the long term, Professor Visvader’s research has the potential to provide more options to people carrying a BRCA1 mutation than risk-reducing mastectomy. It could guide more personalised and effective treatment plans, and could have a positive impact for the wider breast cancer community affected by TNBC.

If proven effective, the team’s findings on the new combination therapy could form the basis of early phase clinical trials – knowledge that could inform future treatments. Ultimately, this research could reduce deaths for people diagnosed with BRCA1-related breast cancer.

Grant code: 2025/RPG0073
Active years: 2026-2029
Scientific project title: Uncovering Targetable Pathways for the Treatment of Early Breast Cancer Arising in BRCA1-Mutation Carriers