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Women with triple negative breast cancer lack the targeted treatments that are available for other types of breast cancer – for example, aromatase inhibitors for ER-positive breast cancers, or Herceptin for HER2-positive breast cancer.
The hope of scientists working in this area, including those funded by Breast Cancer Now, is to develop brand new targeted treatments for triple negative breast cancer. But it’s also vitally important that we identify which patients will benefit the most from the drugs that already exist.
One such group of drugs is chemotherapy, a cornerstone treatment in breast cancer, especially for women with triple negative. However, chemotherapy has a reputation for horrible side-effects which can have a big effect on everyday life for patients. For that reason, compared to ‘smarter’ targeted therapies, chemotherapy is often seen as a blunt instrument - a sledgehammer to crack a nut.
But every tool has its purpose – so what if a sledgehammer was the right tool for the job? What if, for a certain group of women with breast cancer, the right chemotherapy drug was perfectly suited to treat their cancer? Could a chemotherapy drug ever be considered a ‘targeted’ therapy?
Professor Andrew Tutt, who leads the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research and our Research Unit at King’s College London, certainly thinks so - and he has the evidence to back it up. The long-awaited final results of the “Triple Negative Trial ” (TNT), a clinical study jointly funded by Breast Cancer Now and Cancer Research UK, have been published in the journal Nature Medicine.
The Triple Negative Trial was set up by Professor Tutt to investigate whether women with triple negative breast cancer whose cancer had spread would be better off receiving a chemotherapy drug called carboplatin, rather than docetaxel, the chemotherapy they would typically receive.
Professor Tutt and colleagues had good reason to suspect that carboplatin could be very effective for a specific group of patients – those who carry mutations in either the BRCA1 or BRCA2 genes. This is because the type of damage caused by carboplatin, and other ‘platinum’ chemotherapies like it, can normally be repaired with the help of the BRCA1 and BRCA2 proteins.
But tumours with changes in either of the BRCA genes (which contain the instructions to make the BRCA1 and 2 proteins) are much less able to repair this damage, meaning the cancer cells stop multiplying and die. Research in the lab has backed up this theory that cancer cells with BRCA mutations are very sensitive to carboplatin and other drugs like it – so it was time to see whether the same was true in patients.
Starting in 2008, nearly 400 women from across the UK took part in the Triple Negative Trial, made up of patients with triple negative breast cancer whose disease had spread throughout the body. Alterations in the BRCA genes are often associated with triple negative breast cancer, so the researchers wanted to study the effects of these chemotherapy drugs amongst a wider group of women with triple negative disease, rather than just BRCA mutation carriers. Half of these women received docetaxel as they would have done normally, and the other half received carboplatin.
As expected, for the majority of participants, who did not carry a BRCA mutation, it made no difference whether they received carboplatin or docetaxel – about a third of them saw their tumours shrink in response to chemotherapy.
But for the women who carry a BRCA mutation (about 10% of the participants in this study), carboplatin made a big difference: 68% of them saw their cancer shrink in response to carboplatin, more than twice as many as did amongst those who received docetaxel (33.3%).
What’s more, carboplatin delayed the progression of the disease by 6.8 months, compared to 4.4 months with docetaxel – representing around two and half months of extra time for these women before their disease got worse.
Side-effects are a big concern for many people with breast cancer, particularly those with secondary breast cancer, who hope to maintain a good quality of life whilst their treatment continues. So it was reassuring that, although the side-effects caused by both drugs were as expected, the patients receiving carboplatin experienced fewer severe, potentially life-threatening, side-effects compared to those receiving docetaxel.
It’s exciting that thanks to this study, we are now able to identify women with triple negative breast cancer who could benefit from carboplatin – which happens to be a cheaper option compared to docetaxel. It’s even more exciting that these women can be identified with a genetic test for a BRCA mutation – something that is also relatively inexpensive and already widely available throughout the world.
The task at hand now is to ensure that this discovery reaches patients as soon as possible. In direct response to the TNT results, the European Society of Medical Oncology (ESMO) recently made two changes to their guidelines to doctors for the treatment of secondary breast cancer. Firstly, that BRCA-mutated triple negative secondary breast cancer is treated with a platinum chemotherapy like carboplatin, which TNT demonstrated is more effective for these patients.
But crucially, the guidelines also now recommend that women with triple negative secondary breast cancer are offered BRCA gene testing, in order to identify more women who could benefit from platinum chemotherapy.
In a testament to the impact of Professor Tutt’s work for patients with triple negative breast cancer, the ESMO guidelines stated that the TNT study was “probably the largest achievement of the last two years” in research into secondary triple negative breast cancer.
We hope that guidelines here in the UK will be updated as quickly as possible, and we have called on NICE to include carboplatin in their guidelines on advanced breast cancer and NHS England to consider issuing commissioning advice to help ensure carboplatin is used routinely to treat the patients who could benefit.
Triple negative breast cancer has traditionally lacked targeted treatments and had poorer survival rates compared to other forms of the disease. But thanks to research supported by Breast Cancer Now and others, we’re starting to see some real tangible progress for women with BRCA mutated breast cancer, which is often associated with triple negative disease.
Recently, it has been shown that olaparib, a PARP inhibitor drug which Breast Cancer Now scientists helped to discover, could delay the progression of secondary breast cancer in women with BRCA gene mutations. Now the results from TNT, a study made possible with Breast Cancer Now’s support, show that the same women could also benefit from carboplatin.
Of course, there’s much more work to do for the benefit of all women with triple negative breast cancer. But through a similar combination of developing brand new drugs and using existing treatments more cleverly, our scientists are working hard to ensure that everyone gets the treatment they need.
Read the study abstract for the Triple Negative Trial on Nature Medicine.
The coronavirus pandemic has put a lot of our lab-based research on hold. But we don’t want to lose momentum or to let progress stall. We need your support, now more than ever, so that our researchers can make up for lost time.
Breast Cancer Now thanks Walk the Walk for their very generous support towards Professor Andrew Tutt’s work. You can find out more about them below.
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