Aggressive breast cancer 'switch' identified

Australian researchers have identified a gene that drives an aggressive form of breast cancer, and they hope to find a way to "switch it off".

The study's main finding that a gene known as "inhibitor of differentiation 4" (ID4) not only "marks" but appears to control the highly aggressive form of triple negative breast cancer was published online in the journal Nature Communications.

"We found that ID4 is produced at high levels in roughly half of all triple negative breast cancers," said project leader Alex Swarbrick from the Garvan Institute of Medical Research in Sydney.

The researchers found that triple-negative breast cancers have two forms that likely originate from different cell types. This helps explain why survival prospects for women with the diagnosis tend to be either very good or very bad.

The aggressive form of triple-negative breast cancer appears to arise from stem cells, while the more benign form appears to arise from specialised cells.

The gene ID4 determines whether a stem cell remains a stem cell, or whether it differentiates into a specialist cell.

The researchers found that when the high levels of ID4 in a stem cell are "switched off", other genes that drive cell specialisation are "switched on".

"We showed that if you block the ID4 gene in experimental models of triple negative breast cancer, the tumour cells stop dividing," Swarbrick said.

It is interesting to note that blocking ID4 "switches on" the oestrogen receptor3 and several other genes expressed by the milder form of breast cancer.

"Oestrogen receptor-positive breast cancers have a relatively good prognosis because the drug Tamoxifen is very effective at blocking the oestrogen receptor and hence their growth," Swarbrick added.

"We speculate, therefore, that by blocking ID4 it might be possible to turn stem cell-like breast cancers into less aggressive breast cancers that may even respond to Tamoxifen," he said.