Triple negative breast cancer

Triple negative breast cancer (TNBC) is a rare but aggressive type of breast cancer, accounting for around 15% of cases. This cancer type is most commonly seen in women under 40, and it can very rarely also develop in men.

A lack of treatments

As TNBC generally occurs in younger women who are below the age for regular breast screening, tumours are often not discovered until they have progressed and spread to other parts of the body, making treatment more difficult. If caught in its early stages, TNBC can often be successfully treated using surgery and radiotherapy. However, if TNBC is diagnosed later after it has already spread, treatment is much more difficult, and the survival rate is much lower.

Common treatments for less aggressive types of breast cancer, such as hormone therapy, are not suitable so alternatives including surgery, chemotherapy, radiotherapy and immunotherapies are used instead but aren’t always successful. TNBC grows and spreads very quickly and often recurs after treatment, so new treatments are needed to improve the prognosis for TNBC patients who are diagnosed at a late stage, when less options are available.

Replacing the ‘gold standard’ in breast cancer research

Most breast cancer research is carried out using either genetically modified mice, or mice that have had cells with cancer-specific mutations injected into them, causing them to grow tumours. As the tumours grow, the animals likely experience pain and discomfort before they are killed so the tumour can be studied. This is the ‘gold standard’ practice and hundreds of thousands of animals are used each year, but while these mice can model some aspects of human cancer, the results don’t always directly translate into findings for humans.

Transitioning to animal-free methods

Dr Cinzia Allegrucci at the University of Nottingham has developed a new human cell-based model of TNBC, using 3D ‘cell balls’ called organoids. These organoids are generated from human induced pluripotent stem cells (iPSCs – special cells that can be ‘reprogrammed’ to turn into any cell type) which have been given TNBC-specific mutations using gene editing technology.

These organoids closely resemble human breast tissue and show the characteristic features of TNBC, including increased and uncontrolled cell growth.

This organoid model offers several advantages over traditional animal experiments. Firstly, it provides a more accurate representation of human TNBC, allowing researchers to study the disease’s early stages and progression in a human-relevant context. Secondly, it enables the testing of new therapies specifically designed for TNBC, which has unique genetic mutations and lacks the three common receptors targeted by other breast cancer treatments. This approach not only improves the relevance of the research to human patients but can also replace animal testing, potentially speeding up the development of safe and effective treatments

An animal-free success story

Cinzia’s lab previously used around 50 mice per year to carry out TNBC research, but over the past few years she has successfully replaced mice in her work by developing her organoid model.

Common methods to grow organoids involve the use of scaffolds to support the cells as they grow, usually Matrigel (a product derived from mouse tumours). At least one mouse is used to create just two tubes of Matrigel, and Cinzia estimates that her cancer unit and lab use around 100 tubes of Matrigel per year. In this project, Cinzia will develop new animal-free synthetic scaffolds to replace Matrigel in her work, saving the lives of at least 50 mice per year, while many more mice could be saved if others also begin to use her animal-free methods.

Cinzia is keen to widely share her methods and resources to encourage others to adopt these animal-free techniques. She will achieve this by engaging with researchers, patients, the public and pharmaceutical companies, while also training the next generation of young scientists to champion animal-free approaches.