In a new study, researchers from the UK have discovered a novel gene that, when mutated, can drive development and progression of triple-negative breast cancer - an aggressive form of the disease that accounts for 10-20% of breast cancers.
As such, triple-negative breast cancer does not respond to hormone therapy, meaning individuals with this subtype have a poorer prognosis than those with other subtypes. Basal cell breast cancer is the most common form of triple-negative breast cancer.
The study researchers - including joint first author Dr. Walid Khaled of the Welcome Trust Sanger Institute and the University of Cambridge in the UK - note that scientists are in the process of investigating new ways to treat triple-negative breast cancer. Much research has focused on identifying genes associated with the condition, though to date, very few have been found.
For this latest study, published in the journal Nature Communications, Dr. Khaled and colleagues took a different approach to identifying such genes; they assessed alterations to genes that influence the actions of stem cells and developing tissues, as past research from the team has indicated that these alterations affect cancer development.
Reducing BCL11A activity found to reduce cancer-like behavior
By assessing these gene alterations among breast cancer cells from nearly 3,000 patients, the team found that a gene called BCL11A was particularly active in triple-negative breast cancer.
- Triple-negative breast cancer is more likely to occur before the age of 40 or 50, while other breast cancers are more common among people over the age of 60
- People with a BRCA1 gene mutation are at increased risk of triple-negative breast cancer
- Treatment for triple-negative breast cancer usually involves a combination of surgery, radiation therapy and chemotherapy.
Increased BCL11A activity was identified in around 8 out of 10 basel-like breast cancers and was associated with more aggressive tumors, according to the researchers. "Our gene studies in human cells clearly marked BCL11A as a novel driver for triple-negative breast cancers," says Dr. Khaled.
The researchers then set out to see how both human and mouse breast cells reacted when they introduced an active BCL11A gene. They found that this caused the breast cells to act like cancer cells.
What is more, when the team reduced BCL11A activity in three samples of human triple-negative breast cancer cells, they found that these cells lost some cancer-like characteristics. When these cells were introduced to mice, they were less likely to drive tumor growth.
"So by increasing BCL11A activity we increase cancer-like behavior; by reducing it, we reduce cancer-like behavior," explains Dr. Khaled.
This finding was confirmed with further experiments in mice; when the rodents' BCL11A genes were inactivated, tumor growth was stalled in their mammary gland. Mice that did not have this gene inactivated, however, developed tumors.
In addition, the researchers found that BCL11A is important for the normal development of breast stem cells and progenitor cells. Past studies have shown that mutations in these cells may drive the development of basel-like cancers.
Commenting on their findings, study author Prof. Carlos Caldas, of the University of Cambridge and the Cancer Research UK Cambridge Institute, says:
"This exciting result identifies a novel breast cancer gene in some of the more difficult-to-treat cases. It builds on our work to develop a comprehensive molecular understanding of breast cancer that will inform clinical decisions and treatment choices.
Finding a novel gene that is active in cancer should also help in the search for new treatments."
Earlier this month, Medical News Today reported on a study by researchers from the Mayo Clinic suggesting that women with atypical hyperplasia - an accumulation of abnormal cells in the breast ducts or lobules - may have a high lifetime risk of breast cancer.