A preventive treatment could prove effective on women who carry the mutated BRCA1 breast cancer gene, greatly reducing their chances of developing the disease, scientists have said. They have identified a protein marker associated with pre-cancerous cells that could be targeted by existing drugs.
Women with the BRCA1 gene have an elevated risk of developing an aggressive form of breast cancer. Yet, very few options exist today to avoid them falling sick. Many of them currently choose to have their breast tissues and ovaries surgically removed.
The aim of the study, published in Nature Medicine, was to identify other potential treatments that do not involve surgery.
The researchers looked at breast tissue to better understand the mechanisms behind the growth of cancerous cells and how to block them.
A protein called Rank
The team from the Walter and Eliza Hall Institute in Australia analysed samples donated by women with the BRCA1 gene after they had undergone surgery.
The researchers isolated a specific type of breast cell that is mapped by a protein receptor known as "rank". They believe this type of cells is a cancer precursor-cell as it appears to have many similarities with aggressive breast cancer cells.
"These cells proliferated rapidly, and were susceptible to damage to their DNA − both factors that help them transition towards cancer. We believe these are the cells that are most likely to develop into cancer cells in the breast tissue of these women," explains study co-author Emma Nolan. "We were excited to discover that these pre-cancerous cells could be identified by a marker protein called rank."
The discovery is particularly exciting because existing drugs already target the rank signalling pathway. "The identification of rank on the surface of these cells meant that we could try to inactivate these cells before they became cancerous. Using an inhibitor rank signalling called denosumab − which is clinically available − we were able to switch off these precancerous cells at a very early stage," said co-author Geoff Lindeman.
In pre-clinical trials, the scientists were indeed able to show that denosumab – which usually is used to treat osteoporosis − could prevent or delay tumours from forming.
The next step will be to hold clinical trials to see if high-risk women with the BRCA1 mutation could be well-protected by this drug.
"By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation," co-author Jane Visvader concluded. "It is very exciting to think that we may be on the path to the 'holy grail' of cancer research, devising a way to prevent this type of breast cancer in women at high genetic risk."