Researchers discover gene switch to tame aggressive breast cancers

March 30th, 2015


NBCF-supported researcher Dr Alex Swarbrick and his team from Sydney’s Garvan Institute of Medical Research have made a significant discovery which has the potential to turn aggressive breast cancers into easy-to-treat tumours with the flick of a ‘gene’ switch.

The research, published this week in the prestigious journal Nature Communications, has found that the difficult-to-treat, triple-negative breast cancers are actually two distinct diseases that originate from different cell types. This helps to explain why survival prospects for women with this sub-type of breast cancer tend to be either very good or very bad.

The more aggressive form of triple-negative breast cancer appears to arise from stem cells – which have the ability to change and spread into other tissue very easily.

Previous studies have shown that breast stem cells are needed for breast growth and development during puberty and pregnancy, but little has been know about what causes stem cells to mature into more specialised cells. This new study builds on existing knowledge, discovering that a gene known as ‘inhibitor of differentiation 4’ (ID4) determines whether a stem cell remains a stem cell, or whether it matures.

Dr Swarbrick and his team have identified that ID4 is also the ‘master switch’ that appears to control the growth and development of the aggressive form of triple-negative breast cancer arising from stem cells.

“We found that ID4 is produced at high levels in roughly half of all triple-negative breast cancers, and that these cancers have a particularly poor prognosis,” said Dr Swarbrick. “We also showed that if you block the ID4 gene in experimental models of triple-negative breast cancer, the tumour cells stop dividing.”

Blocking the ID4 gene not only stops the triple-negative breast cancer cells from dividing, but it also appears to switch on oestrogen receptors on the surface of these cancer cells. Breast cancers that test positive for oestrogen receptors have a relatively good prognosis because they can be treated effectively with existing drug, tamoxifen.

“We speculate, therefore, that by blocking ID4 it might be possible to turn stem-cell-like [triple-negative] breast cancers into less aggressive breast cancers that may even respond to tamoxifen,” Said Dr Swarbrick. “If we are correct, that would be remarkable.”

For women like NBCF Community Ambassador Louise Sinclair, who was diagnosed with triple negative breast cancer while pregnant with her fourth child, this development could lead to much more effective treatments and better outcomes.

“It [research] really is our most effective way of treatment and finding the answers to breast cancer,” said Ms Sinclair.

The next step for Dr Swarbrick and his team will be to study the biochemistry of ID4 in a cell – to determine how best to block it in people. It is hoped that these findings will lead to more effective and personalised treatments for women with triple-negative breast cancer.

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Dr Alex Swarbrick currently holds a National Breast Cancer Foundation Infrastructure Grant with Associate Professor Robin Anderson. This infrastructure grant supports the development of a new national repository of primary and metastatic human breast cancer tissue for a range of research purposes.

Read more about this current NBCF grant here: “Repository of primary tumours and metastases from breast cancer patients”