Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain

Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain
Professor Nicola Sibson of the Department of Oncology has been awarded a grant worth almost £200,000 by research charity Breast Cancer Now to fund cutting-edge research to uncover novel treatment combinations to control breast cancer that has spread to the brain.
The news comes on Secondary Breast Cancer Awareness Day (Friday 13th October 2017), as leading charity Breast Cancer Now announces more than £700,000 of funding across the UK for research specifically targeting secondary (or metastatic) breast cancer – where the disease has spread to another part of the body.
When breast cancer spreads, known as secondary or metastatic breast cancer, it becomes incurable. While metastatic breast cancer can sometimes be controlled using different combinations of treatments, it cannot be cured, and almost all of the 11,500 women that die as a result of breast cancer each year in the UK will have seen their cancer spread. Nearly 600 women in Oxfordshire are diagnosed with breast cancer every year, and over 100 women in the region die from the disease each year.1
The brain is protected by its own security system, a structure called the blood-brain barrier (BBB). The BBB acts as a filter, preventing harmful substances from reaching the brain. However the virtually impenetrable nature of the BBB makes delivery of drugs to the brain extremely difficult, meaning there are few effective treatments for breast tumours that have spread to the brain (brain metastases).
Up to a third of patients with secondary breast cancer have seen their cancer spread to the brain. This can cause varying problems with brain function depending on which areas the breast cancer cells have spread to, and can often severely affect a patient’s quality of life, with debilitating symptoms such as changes in mood or behaviour, seizures, headaches, vomiting and uncoordinated movement.
Professor Sibson, Professor of Imaging Neuroscience at the CRUK/MRC Oxford Institute for Radiation Oncology has previously found that one element of the immune system, the inflammatory response, is important in the spread of breast cancer to the brain. Her team has previously found that certain inflammatory molecules are present at higher levels in brain metastases, and may be key drivers of tumour growth.
With funding from Breast Cancer Now, Professor Sibson and her team will undertake a three-year project to pinpoint which combinations of anti-inflammatory drugs, which are able to cross the BBB, reduce the growth of breast tumours in the brain most effectively, and whether these could also be given alongside radiotherapy with greater effect.
Professor Sibson said “We urgently need to find ways to treat brain metastases more effectively and improve survival rates. With this funding from Breast Cancer Now our aim is to increase treatment options for patients suffering metastatic spread to the brain. We hope that by targeting the innate immune system we can halt or reduce tumour growth, and enhance the effectiveness of radiotherapy.”
The scientists will first implant breast tumours into the brains of mice, before testing a range of anti-inflammatory drugs and examining the effect on tumour growth. The team will then combine the most effective anti-inflammatories with radiotherapy in mice to identify which combinations best control tumour growth in the brain. The researchers hope to identify new ways to predict which patients are most likely to benefit from anti-inflammatory drugs and radiotherapy. In addition, the team will explore how another component of the inflammatory response, adhesion molecules, are involved in tumour growth, and whether targeting these directly could also be an effective treatment strategy.
Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now said “Professor Sibson’s research could pave the way for new treatment combinations that could halt tumour growth in men and women whose breast cancers have sadly spread to the brain. Anti-inflammatory drugs are already used to treat arthritis – and if these new combinations are found to be effective, these drugs could be made available for treating patients with brain metastases much more quickly.
“It is essential that we find new ways to treat secondary breast cancer in the brain – to improve quality of life and chances of survival for those living with this debilitating disease.
“Our ambition is that by 2050, everyone who develops breast cancer will live. But if we are to achieve this, we desperately need to raise funds for research to find ways to stop the disease spreading. Professor Sibson’s project could help bring us one step closer to our 2050 vision and we’d like to thank our supporters across Oxford who continue to help make our world-class research possible.” 
Fiona Leslie, 49 from Aylesbury, is living with incurable metastatic breast cancer. Having first been diagnosed with breast cancer in 2013, Fiona underwent a mastectomy, radiotherapy and chemotherapy, before learning that her breast cancer had unfortunately spread to her lungs and her spine.
In April 2015, Fiona began receiving revolutionary drug Kadcyla, which kept her disease at bay for over two years, and enabled her to live a relatively normal life in the meantime. However in June 2017, scans showed that Fiona’s breast cancer had spread to her brain.
1. Local incidence and mortality survival statistics were provided on request by Public Health England, April 2017.

John Findlay wins Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) Prize

The CRUK Oxford Centre is delighted to announce that the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) recently awarded Centre member, John Findlay, its prestigious British Journal of Surgery prize for the best free paper presented at the 2017 AUGIS Scientific Meeting in Cork, Ireland. John is a Specialty Registrar in General Surgery in the Oxford Deanery, and a Senior Clinical Research Fellow in OesophagoGastric Surgery informatics at the NIHR Oxford Biomedical Research Centre.
The prize was awarded for his paper ’Staging gastric cancer with 18F-FDG PET-CT identifies frequent unsuspected metastases and patients of high risk of incurable disease, early recurrence and death’.
This study included 279 consecutive patients with stomach cancer (non-junctional gastric adenocarcinoma) who as part of their treatment at Oxford University Hospitals NHS Foundation Trust underwent a staging PET-CT scan. At present, there is little evidence that routinely using PET-CT in this context is useful. Consequently, it is not recommended by national and international guidelines. However, the Oxford OesophagoGastric Centre has routinely used cutting edge 18F-FDG PET-CT scanning technology for both oesophageal (gullet) and stomach cancer for more than 10 years. The test uses radio-labelled glucose molecules, which tend to concentrate in cancer tissues. These tissues then become visible, or ‘avid’, on the scan and may help provide information about the behaviour of cancer.
In the largest and most contemporary series to date, PET-CT was shown to detect incurable or metastatic cancer in approximately 7% of patients, despite their preceding CT scan being clear. Furthermore, the subgroup of patients who also had avid lymph nodes appeared to be at increased of such incurable disease, and also early cancer recurrence and death after surgery. This builds on previous findings from John’s research in oesophageal and gastro-oesophageal junctional cancer, and suggests PET-CT should also be considered routinely for patients with gastric cancer.
John is now exploring whether PET-CT should also be repeated before surgery if patients receive chemotherapy, and whether the response of avid nodes to this chemotherapy allows clinicians to monitor its effectiveness. He commented that he was honoured to receive this prize on behalf of his collaborators, and hopes that these findings will be able to improve staging and counselling for patients with stomach cancer, and also help identify patients who might benefit from additional investigations.