Secondary breast cancer, when breast cancer spreads to other parts of the body, can have a huge impact on a person’s health and quality of life, and is the cause of almost all of the 11,500 breast cancer deaths every year in the UK.
It’s therefore absolutely essential that we find ways to stop the spread of breast cancer. To do this, we need to find ways to predict who is most likely to see their breast cancer spread, so that they can receive the best possible treatments to try and prevent this happening.
Traditionally, to predict whether breast cancer will spread, doctors have used tools based upon the features of the primary tumour, like the size of the tumour and whether it has already invaded nearby lymph nodes.
However, a team involving Breast Cancer Now-funded researchers at our Research Unit at King’s College London (KCL) are working on a new method, which could help doctors see more clearly into the future. They are using an imaging technique which could detect changes in the lungs before any secondary tumours are visible.
Here we discuss this research, published in the journal Theranostics and led by Professor Tony Ng’s team at KCL with colleagues from University College London and Münster in Germany, which highlights the important role that the immune system has in the spread of breast cancer.
The immune system: a double-edged sword
We often think of the immune system as our body’s flawless protector, defending us against threats from the outside like a knight in shining armour. However, the immune system can also play a part in illness too.
This is because the immune system is not one unified force, it’s more like a coalition of different factions that are constantly coming together and falling apart, collaborating and keeping each other in check. Normally, this helps ensure that responses to real threats are appropriate – that the immune system doesn’t overreact against relatively harmless opponents, or continue the attack long after the threat has gone.
But this also provides a perfect opportunity for cancer to exploit the immune system for its own aims. Inflammation is a process familiar to anyone who has scraped their knee: the damage and invasion of germs causes immune cells to flock to the area, causing blood vessels to grow and skin to be repaired, becoming red and swollen. But this very same process can also be hijacked by tumours to help themselves grow and spread to other parts of the body.
Gathering a perfect storm
Our research team from KCL knew that a group of immune cells called ‘myeloid-derived suppressor cells’ (MDSCs) had a role in the spread of breast cancer to the lungs. These suppressor cells gather in the lung, and hold back other immune cells which might normally attack a cancer. They also cause inflammation which prepares the environment in the lung, making it a favourable location for cancer cells to spread to and grow into tumours.
The message that MDSCs use to muster in the lungs is S100A8/A9, a protein duo made up of S100A8 and S100A9. This message is released by MDSCs, which then attracts more of their kind, which in turn produce more S100A8/A9, perpetuating a vicious cycle.
Seeing is believing
However, if S100A8/A9 is the key to this process, the team guessed that if you could make S100A8/A9 visible, you could identify where and when the lungs were preparing to be colonised by breast cancer cells.
To test this theory, they developed a radioactive ‘tracer’ molecule which attaches itself to S100A9, and can be detected using a special scan called SPECT (single photon emission computed tomography). The tracer releases radiation which can be detected by the SPECT scanner, highlighting areas where S100A8/A9 molecules, and MDSCs, are accumulating.
In this study partly funded by Breast Cancer Now, the researchers tested the S100A9 tracer in mice that carry cells from mouse mammary tumours, the mouse equivalent of human breast cancer. They showed using a miniature SPECT scanner that the tracer lit up the lungs of mice well before any breast tumours were visible in the lung. What’s more, the tracer was able to distinguish between a breast cancer cell line which has the tendency to spread to the lung, and one that is relatively less aggressive and doesn’t spread.
SPECT scan showing the radioactive tracer ‘lighting up’ the lungs where special immune cells (MDSCs) are accumulating, priming the lungs for the arrival of migrating breast cancer cells and formation of secondary tumours. The left set of images show the lungs of mice without breast cancer, and the right set shows the lungs of mice which had been injected with aggressive breast cancer cells. Image credit: M. Eisenblaetter, F. Flores-Borja, et al. Available via Open Access at thno.org.
The researchers also investigated in more detail how MDSCs are recruited to the lungs, and how they repress the anti-cancer activities of other immune cells, further extending our knowledge of the role that the immune system plays in the spread of breast cancer.
Peering into the future
Though this is an early study in mice, the team are really encouraged by the results. The prospect of a hospital scan which could predict whether breast cancer will spread to the lungs is exciting, though the team have a lot more work to do before this could be tested in humans. The next step is to develop a more effective S100A9 tracer molecule, better suited for use in breast cancer patients, which can be tested in clinical trials in the future.
The more immediate outcome of the study is that it provides a new method to help researchers unpick how the immune system is involved in the spread of breast cancer. This could be used to develop new treatments called immunotherapies, which encourage the immune system to attack breast cancer cells in a variety of ways.
Anything that could provide breast cancer patients and their doctors with a more accurate picture of whether their breast cancer will spread will help tailor treatments to stop this from happening – and ultimately help to ensure that everyone diagnosed with breast cancer will live.
Breast Cancer Now thanks the Sarah Greene Tribute Fund and Walk The Walk for their generous support of Prof Tony Ng’s and Prof Andrew Tutt’s work, respectively, at the Breast Cancer Now Research Unit at King’s College London.