A new biomarker could predict whether a common type of chemotherapy will be effective for patients with ‘triple negative’ breast cancer and help to personalise their treatment, new research has found.

The study, funded by Breast Cancer Now, found that breast tumours with higher levels of a protein called NUP98 were associated with a poorer response to anthracycline-based chemotherapy, and therefore worse survival outcomes.

It is hoped the findings could lead to a simple test for NUP98 levels that could be implemented in NHS hospitals without the need for specialist equipment – helping to identify patients who are unlikely to benefit from anthracycline chemotherapy and should be given an alternate form of treatment.

Over 8,000 women in the UK each year are diagnosed with triple negative breast cancer – a diverse group of cancers which often have poor outcomes and lack the key receptors that can be targeted in other forms of the disease. As a result, triple negative patients are often reliant on chemotherapy as their main treatment in addition to surgery.

Anthracyclines are a group of chemotherapy drugs commonly used in treating triple negative breast cancer. While these drugs can be highly effective for some patients, they may not work for others, with relapses in triple negative patients being very common within three years of diagnosis.

In particular, it is thought that patients’ survival chances may be closely linked to their response to first-line chemotherapy. A recent study found that three-year survival for patients who had seen pathological complete response to chemotherapy before surgery (where no signs of cancer were left in tissue samples after treatment) was 88%, compared to just 68% for patients who had residual disease after therapy.

This association between response to first-line treatment and patients’ survival demonstrates the need to find ways to predict response to chemotherapy, to ensure patients receive the most effective drug for them as early as possible.

In a new study published in BMC Cancer, researchers at Queen’s University Belfast used patient tissue samples to identify genes whose high or low activity was associated with clinical outcomes in triple negative breast cancer – finding higher levels of NUP98 gene activity in patients who had poorer outcomes.

The team, led by Dr Niamh Buckley at Queen’s University Belfast, analysed tissue samples from over 100 patients with triple negative breast cancer who had received FEC chemotherapy, alongside data regarding their treatment plans and clinical outcomes – as well as tissue samples from 40 healthy women.

High levels of the NUP98 protein were found to be significantly linked to poor response to anthracycline chemotherapy, with the highest production of NUP98 being associated with the worst survival outcomes – identifying NUP98 as a novel biomarker to predict treatment response. Patients with the highest levels of NUP98 were found to be approximately nine to ten times more likely to relapse following treatment with anthracyclines.

The researchers compared their observations to global breast cancer data – finding that NUP98 levels were only linked to survival if patients had received chemotherapy, and specifically anthracycline-based chemotherapy. NUP98 levels were found not to predict response to taxane-based chemotherapy.

Importantly, the researchers also found that levels of this protein in patient’s tumours could be detected reliably using a pathology technique that is already standard practice in NHS hospital laboratories called immunohistochemistry.

The researchers now hope to verify these findings in a larger prospective cohort, paving the way for trials to assess whether a test for NUP98 levels could guide the use of anthracycline chemotherapy in triple negative breast cancer and ensure patients get the most appropriate treatment.

With the researchers also finding that the production of NUP98 was significantly higher in both invasive tumours and an early form of non-invasive breast cancer known as DCIS (ductal carcinoma in situ) compared to healthy breast tissue, it is hoped that testing for this novel biomarker could also prove useful in the early detection of the disease. 

Lead author Dr Niamh Buckley, Breast Cancer Now Fellow at the School of Pharmacy, Queen’s University Belfast, said:

Our study identifies NUP98 as a novel biomarker to predict response to anthracyclines in triple negative breast cancer. The ability to prospectively identify patients who are less likely to respond to standard of care chemotherapy could now be a vital step in improving the overall survival of these patients.

It is essential that we find ways to tailor treatment for patients with triple negative breast cancer. While we know some women respond very well to the current treatment, others receive very limited clinical benefit and experience all of side effects associated with chemotherapy.

Our findings will hopefully help us identify women who should be considered for an alternate treatment option and help direct future research to develop new therapies for all women with triple negative breast cancer.

Baroness Delyth Morgan, Chief Executive at Breast Cancer Care and Breast Cancer Now, which funded the study, said:

This is a very promising discovery. It’s really encouraging that testing for levels of NUP98 could help ensure patients get the type of chemotherapy that’s most likely to be effective for them as early as possible.

Anthracycline chemotherapy is a cornerstone of treatment for triple negative breast cancer, but it’s so important we identify patients that will not benefit from it so that they can be given other more effective therapies as soon as possible.

With triple negative patients still severely lacking in targeted treatments, it remains one of the greatest areas of unmet need in breast cancer and we urgently need to find new and kinder options to help stop more women dying.

We look forward to further research to verify these findings and develop a useful test for NUP98 levels in the clinic, to help ensure all patients get the most effective therapies for them. By trying to tailor chemotherapy treatment in this way, we hope these findings could in future help improve the outcomes of patients with more aggressive and hard-to-treat forms of the disease.