Thanks to early detection and advances in treatment, breast cancer survival rates have improved significantly in recent years.
However, existing therapies have limited benefit if the disease metastasises or spreads to other sites in the body.
Breast cancer metastasis to the brain causes considerable morbidity and is inevitably fatal, with patients typically surviving four to eighteen months from diagnosis.
Researchers at UQ’s Faculty of Medicine are combining their world-leading expertise in a multifaceted approach to try to improve that outlook for patients.
Head of the Molecular Breast Pathology team at UQ’s Centre for Clinical Research, Professor Sunil Lakhani, says it is clear we need to be more innovative in our approach to treating these brain tumours – because they resist existing therapies.
Professor Lakhani’s team collaborates with scientists around the globe to tackle important and complex questions about breast cancer development at the molecular and cellular level.
For their latest project, they have joined with UQ’s School of Pharmacy to develop cutting-edge research into the spread of breast cancer to the brain. The three-year study builds on previous research suggesting the movement of calcium in cells goes awry in both primary breast cancers and in metastatic tumours in the brain.
Understanding how these processes are altered in breast cancer could lead to new ways to reduce the chance of the disease spreading, and arrest the growth of metastatic tumours once they are detected.
The US Department of Defense has committed more than A$1.3 million to the project through its Breast Cancer Breakthrough Scheme. This is the only research outside North America to receive such funding.
Dr Jodi Saunus is working alongside Professor Lakhani to improve breast cancer management and survival rates for women.
The multidisciplinary researcher is leading a new clinical trial – ‘BoNSAI’.The study is expected to provide major advances in understanding the dose of drugs needed to target tumours in the brain. The brain is normally protected from intravenous drugs by unique, impenetrable blood vessels.
While the vessels that grow through tumours are ‘leakier’ than the rest of the brain, they are still not as permeable to drugs as blood vessels elsewhere in the body. The degree to which this blocks the effects of cancer drugs in metastatic brain tumours is hotly debated in scientific literature.
By using cutting-edge medical imaging – made possible by the launch of the Herston Imaging Research Facility – the BoNSAI study will determine how much of a drug administered to breast cancer patients is absorbed into metastatic brain tumours.
“We will attach a PET tracer to a drug routinely used to treat breast cancer,” Dr Saunus explains. “Participants will then undergo two to three scans over the following week or so.
These scans will enable us to see how much of the administered drug actually reaches the tumour and is retained there. Then we can better understand the factors that control this, such as the patterns of blood flow and pressure inside the tumours.
Quality of life for people living with brain tumours can be incredibly poor, so there is a great need for research to improve both manageability and survival rates.”
The research team is hoping to clarify speculation in scientific literature by providing the evidence for guidelines on dosing. This could also provide benchmarking for treatment of metastatic brain tumours originating from cancer types other than breast cancer, such as lung cancer and melanoma.
The BBB aims to collect a tumour sample from every patient undergoing treatment at the Royal Brisbane and Women’s Hospital. It has become a valuable resource for breast cancer research in Australia and abroad.
Molecular genetics specialist, Dr Amy McCart Reed, coordinates the BBB in addition to her research portfolio. “A number of our discoveries would not have been possible without the valuable samples donated by breast cancer patients,” Dr McCart Reed says. “Metastatic brain tumours in particular are not easy to come by.”
BBB samples have supported the ground breaking research into breast cancer genomics, undertaken in collaboration with the International Cancer Genome Consortium.
Centre for Clinical Research Team Leader, Dr Peter Simpson, has published several high impact research papers defining the breast cancer genome, together with collaborators at the Wellcome Trust Sanger Institute in Cambridge. In particular, new research investigating mutational signatures has the potential to identify a subgroup of patients who might benefit from additional therapies.
Professor Lakhani says the study has identified a much larger patient group who could benefit.
Professor Lakhani holds an appointment with Pathology Queensland, and was recognised with the 2016 Robert Sutherland Award for Excellence in Translational Research from the ANZ Breast Cancer Trials Group.
“I’ve been fortunate to lead and work with some amazing research teams. We’ve come a long way in improving women’s health outcomes.”