'Off-switch' for aggressive breast cancers discovered

A team of researchers has found the switch that might tame the most aggressive of breast cancers.

Researchers from Garvan Institute of Medical Research have found that so-called 'triple-negative breast cancers' are two distinct diseases 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 Sydney-based research team has found a gene that drives the aggressive disease and hopes to find a way to switch it off. 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.

Stem cells have many of the same features as cancers. They are plastic and flexible, and have the ability to proliferate and spread into other tissues, deadly traits in cancers.

The new study has shown that a gene known as inhibitor of differentiation 4 (ID4) determines whether a stem cell remains a stem cell, or whether it differentiates into a specialist cell. Notably, when the high levels of ID4 in a stem cell are "switched off," other genes that drive cell specialisation are "switched on."

Researcher Alex Swarbrick said that they 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, adding that they also showed that if you block the ID4 gene in experimental models of triple negative breast cancer, the tumour cells stop dividing.

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, noted Swarbrick.

Swarbrick added that they 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. If they are correct, that would be remarkable.

The study is published online in Nature Communications.