Breast cancer breakthrough as Cambridge University finds gene behind killer disease

Friday 9 January 2015

Cambridge University and the Wellcome Trust’s Sanger Institute have discovered the gene responsible for triple negative breast cancer

Scientists have identified the gene behind one of most aggressive forms of breast cancer in a breakthrough which could bring life-saving new treatments.

Triple-negative breast cancer is one of the most deadly forms of the disease and nearly one quarter of patients diagnosed will not survive for more than five years.

Now researchers at Cambridge University and the Wellcome Trust’s Sanger Institute have found that the BCL11A gene is overactive in eight out of ten patients.

The study opens the door for therapies which suppress the gene and for screening that would pick up the risk early when women still had time to opt for life-saving mastectomies.

“Our gene studies in human cells clearly marked BCL11A as a driver for triple-negative breast cancers,” says Dr Walid Khaled of the University of Cambridge.

“We also showed that adding an active human BCL11A gene to human or mouse breast cells in the lab drove them to behave as cancer cells.

“As important, when we reduced the activity of BCL11A in three samples of human triple-negative breast cancer cells, they lost some characteristics of cancer cells and became less tumorigenic when tested in mice.

“So by increasing BCL11A activity we increase cancer-like behaviour; by reducing it, we reduce cancer-like behaviour.”
Around 10,000 people a year are diagnosed with triple-negative breast cancer. The disease does not respond to traditional breast cancer drugs like Herceptin and is one of the most aggressive types.

Just 77 per cent of people with triple-negative breast cancer will survive for five years, compared with 93 per cent for other types of the disease.

For the new study, researchers looked that the genetic profile of tumours from 3,000 patients, specifically searching for genes which affect how stem cells and tissues develop.

Higher activity of the BCL11A gene was found in approximately eight out of ten patients and was associated with a more advanced grade of tumour.

To test the theory that the gene was promoting tumour growth, scientists genetically engineered mice to have inactive copies. None of the animals went on to develop tumours in the mammary gland, whereas all untreated animals developed tumours.

“This exciting result identifies a novel breast cancer gene in some of the more difficult-to-treat cases,” said Professor Carlos Caldas, Director of the Cambridge Breast Cancer Research Unit at the University of Cambridge.
“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.”

The breakthrough was welcomed by charities who said it could lead to new targeted treatments.

Dr Emma Smith, senior science information officer at Cancer Research UK, said: “Figuring out the genes that play a role in triple negative breast cancer could lead to new ways to tackle the disease so this study is a promising step forward.
“The next steps will be finding out if the gene plays the same role in causing breast cancer in women, and whether drugs can be developed to target the faulty molecules.

“Triple negative breast cancer can be challenging to treat, so research into the biology of the disease is vital to help scientists come up with new treatments.”

Dr Christopher Runchel, Research Officer at Breakthrough Breast Cancer added: “Whilst this investigation and the discovery of a new gene driver for triple negative breast cancer was mostly confined to cell lines and mice, this work could prove promising in the search for new ways to treat this form of the disease in the future “Triple negative breast cancer is particularly aggressive and does not respond to hormonal therapies such as tamoxifen, or targeted drugs like Herceptin. That’s why the hunt for effective treatments is so important and Breakthrough Breast Cancer have long supported research like this.”

The research was published in the journal Nature Communications.


By Sarah Knapton, Science Editor at
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