Triple negative breast cancer may not be as common as other types of breast cancer but it can sometimes be more aggressive, and what’s more, there are fewer treatment options available. To understand why, we’ll first look at how other cancers are treated and why triple negative breast cancer is different.
When determining what type of breast cancer a person has, doctors test for the presence of molecules called ‘receptors’ in breast tumour samples. These are oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
Up to 80% of breast cancers are ‘hormone positive’, which means the cells in the tumour produce lots of ER and sometimes PR, and they are driven to grow mostly by the hormone oestrogen. Roughly 20% of all tumours are ‘HER2 positive’ and overproduce HER2 – sometimes at the same time as ER or PR.
As well as identifying the type of breast cancer, these receptors are also the targets for treatments. Patients with hormone positive breast cancers can be given hormone therapies, like tamoxifen to block ER, or aromatase inhibitors to stop the production of oestrogen. HER2 positive breast cancer can be treated with Herceptin, which stops the HER2 molecule working. These targeted treatments have proved very effective against their particular forms of breast cancer.
However, about 15% of breast tumours do not have any of these three receptors, and so are known as triple negative breast cancer. As a result, people with triple negative breast cancer won’t benefit from targeted treatments, which are designed to target receptors that their cancer cells don’t carry.
This means that there are currently no specific targeted treatments for this form of the disease - but finding such therapies would help to improve survival rates for triple negative breast cancer. In addition, this could also help reduce the dependency on chemotherapy for treatment, which, despite being sometimes more effective for people with triple negative breast cancer, can have severe side-effects.
PIM-pointing a weakness
However, today we announced the results of some exciting research which could potentially provide a much needed targeted treatment for triple negative breast cancer in the future. The work was led by Professor Andrew Tutt, who heads our Research Unit at King’s College London which is solely dedicated to investigating triple negative breast cancer.
Starting by looking at samples from more than 300 triple negative breast tumours (and nearly 2,000 samples from other types as a comparison), they discovered that a molecule called PIM1 was overproduced in triple negative breast cancers, which was a clue that it could be important for this form of the disease – and therefore might also be a potential weakness.
Their suspicions were correct – early experiments with triple negative breast cancer cells grown in the lab showed that these cancer cells were ‘addicted’ to PIM1, and so by reducing the amount of PIM1 that the cancer cells were able to produce, the researchers slowed down their growth.
Prof Tutt then joined forces with Prof Pascal Meier from the Breast Cancer Now Toby Robins Research Centre in London (of which Prof Tutt is also the Director). Prof Meier’s team is interested in the process of cell death – how cells decide to press the ‘self-destruct’ button when they need to, and why cancer cells can’t (or won’t) do this – and their research is helping to find new ways to kill cancer cells.
Together, this research supergroup found that stopping the production of PIM1 meant triple negative breast cancer cells were much more likely to decide to commit cell suicide. This suggested that, in theory, blocking PIM1 could make other treatments more effective.
So to try this idea out, Prof Tutt’s team tested a drug which blocks PIM1 (as well as its cousins PIM2 and PIM3), in mice which were either carrying triple negative breast cancer cells, or samples of triple negative tumours donated by patients. They showed that not only did the drug slow the growth of breast tumours in these mice on its own, it also improved the effectiveness of a chemotherapy drug called eribulin.
A new treatment on the horizon?
Prof Tutt is not the only one interested in the role of PIM1 in breast cancer – a separate research team based at the University of California in San Francisco have also published research today, independently showing similar results from blocking PIM1 in triple negative breast tumours with two other new drugs.
The really exciting thing is that PIM-inhibitor drugs are already being tested in patients with different types of cancer. Prof Tutt is hoping that clinical trials to investigate whether these drugs could be useful for people triple negative breast cancer could start in the next couple of years.
Today’s announcement is a great example of how collaboration can help bring about new discoveries in breast cancer research – collaborations that Breast Cancer Now continue to foster within the breast cancer research community, or between researchers and the pharmaceutical industry to study what could be the drugs of tomorrow.
But more than that, it’s a great example of how supporting long-term research is helping to tackle the big challenges we face. New targeted treatments for people with triple negative breast cancer can’t come soon enough, and whilst there’s a lot of hard work ahead, we’re excited about the impact that today’s research could have for patients in the not-too-distant future.