Researchers at RCSI University of Medicine and Health Sciences and the Beaumont RCSI Cancer Centre have discovered key molecular changes that drive the spread of breast cancer to the brain.

The research findings, published in the journal Cancer Communications ahead of World Cancer Day (4 February), also identified potential new approaches to treating advanced breast cancer in the future.

With the support of Breast Cancer Ireland ambassadors, Professor Leonie Young and colleagues focused on breast cancer brain metastases, where an original cancer in the breast establishes secondary tumours in the brain.

“Metastatic brain disease is a devastating illness that happens in up to a third of patients with advanced breast cancer,” explains Prof. Young, the study’s Principal Investigator and Scientific Director of the Beaumont RCSI Cancer Centre.

“There are currently few treatment options when this happens, and they centre mainly on surgery and radiation treatment. The prognosis is not good for patients, and we urgently need new medicines to help them.”

Research for new ways to treat metastatic brain disease has tended to focus on changes in the DNA of cancerous cells, but Prof. Young took a different approach. She and her collaborators looked at changes in RNA, a type of molecule that helps to control how genes work.

“There had been some evidence that reversible changes in RNA were present in advanced brain metastatic disease,” says Prof. Young. “So we wanted to explore these changes, to understand them better, on the basis that they could potentially be used to indicate how the disease was progressing and possibly represent new targets for treatments to intervene.”

By examining cells in the lab and patient tumours from both the breast and the brain, the researchers mapped the patterns of methylation in RNA, a natural process where the RNA is decorated with chemical structures called methyl groups that affect the way the RNA works. The scientists were able to show that RNA methylation was an essential mechanism that enables the tumour to evolve and progress.

“In this study we mapped the RNA methylation landscape in advanced breast cancer and determined its clinical relevance, and importantly patients and Breast Cancer Ireland ambassadors played a key role in this work,” says Prof. Young.

“Our research showed that targeting this mechanism with drugs called FTO inhibitors that are currently in trial for other cancer types could potentially be significantly beneficial for patients with breast cancer that has spread to the brain. Our hope is that these findings will translate into better outcomes for patients with advanced breast cancer.”

The study was a collaboration between the Endocrine Oncology Research Group at RCSI’s Department of Surgery and Ben May Department for Cancer Research at the University of Chicago, and was funded by Breast Cancer Ireland, Science Foundation Ireland, Breast Cancer NOW and the Irish Research Council.