Denosumab may prevent breast cancer in women with BRCA1 gene mutation

Researchers have discovered that an existing medication, denosumab, may prevent breast cancer in women carrying a faulty BRCA1 gene.

People who carry a faulty BRCA1 gene are at high risk of developing aggressive breast cancer. Currently many women with a gene mutation choose surgical removal of their breast tissue and ovaries to reduce their chance of developing breast and ovarian cancer.

By pinpointing the cells that give rise to breast cancers in women who have inherited a faulty version of the BRCA1 gene, Walter and Eliza Hall Institute researchers have identified that the denosumab may have potential to prevent breast cancer from developing. If confirmed in clinical studies, this would provide a non-surgical option to prevent breast cancer in women with elevated genetic risk.

Using samples of breast tissue donated by women carrying a faulty BRCA1 gene, Ms Emma Nolan, Professor Jane Visvader and Professor Geoff Lindeman were able to pinpoint the cells that give rise to breast cancer.

RANK inhibitors

Cancer precursor cells in BRCA1-mutant breast tissue had many similarities to aggressive forms of breast cancer, said Ms Nolan. “These cells proliferated rapidly, and were susceptible to damage to their DNA – both factors that help them transition towards cancer,” she said. “We were excited to discover that these pre-cancerous cells could be identified by a marker protein called RANK.”

Walter and Eliza Hall Institute researchers (L-R) Professor Geoff Lindeman, Ms. Emma Nolan, Professor Jane Visvader.

Professor Lindeman said the discovery of RANK as a marker of cancer precursors was an important breakthrough, because inhibitors of the RANK signalling pathway were already in clinical use. “An inhibitor called denosumab is already used in the clinic to treat osteoporosis and breast cancer that has spread to the bone,” he said. “We therefore investigated what effect RANK inhibition had on the cancer precursor cells in BRCA1-mutant breast tissue.”

The research team showed that RANK inhibition switched off cell growth in breast tissue from women with a faulty BRCA1 gene and curtailed breast cancer development in laboratory models.

“We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation,” Professor Lindeman said. “A clinical trial has already begun to investigate this further.”