A genetic fingerprint that reveals the breast cancer patients who are at high risk of the deadly spread of the disease has been found, a discovery that also reveals a new target for treatments.
A pattern of gene activity that can predict individual risk for breast cancer metastasis, when the disease disperses through the body, has been found by a team at the National Cancer Institute, Bethesda, Maryland.
The short term use of this discovery will be in diagnostic tests but the team also found that the pattern is controlled by a single gene called bromodomain 4 (Brd4) and by inserting this gene they could suppress tumour growth and metastasis in studies of mice, suggesting that a drug to mimic this effect could help treat the disease.
"These findings are exciting," says Dr Kent Hunter of NCI's Centre for Cancer Research, one of the team that reports the work in the Proceedings of the National Academy of Sciences. "For the first time in mice, we have a candidate gene for what drives an entire gene signature. This should allow a better understanding of the mechanisms underlying cancer progression in humans."
Normal Brd4 activity is involved in important cell processes including cell proliferation and DNA replication. Defects in these processes are well documented in human breast cancer and the new findings indicates that activation of Brd4 reduces tumour growth by influencing the response of tumour cells to signals from the area immediately surrounding the tumour.
Taking the knowledge gained from the mouse studies, Dr Hunter's team identified a set of 379 genes in humans that are similar and found that the level of activation of Brd4 within a tumour was an important determinant of relapse and survival. Brd4 seemed to drive the use of many of the genes present in the signature.
Although the team does not yet know how central this is gene to the spread of the disease, the find did enable the team to predict survival and relapse of breast cancer patients.
"The results of this study and other work in our laboratory suggests that people with inherited differences in Brd4 and the proteins that it induces have a genetic predisposition for developing cancer metastasis," he adds. "A better understanding of this gene may lead to improved methods of diagnosing and treating cancer."
As for when a test could be available, he said that depended on the outcome of more research to establish how often this gene plays a central role in spreading. In the longer term, it may lead to drugs too, but he says much work has to be done to identify those with the right action: "We are currently unaware of any drugs that mimic Brd4."