Australian Researchers Find a Way to Predict Which Breast Cancers Will Spread

Australian researchers have identified a molecular weakness that could eventually help doctors decide which patients with triple-negative breast cancer (TNBC) — an aggressive subtype that lacks the estrogen receptors, progesterone receptors and HER2 protein many other breast cancer treatments target — might benefit from an existing cancer drug that slows the disease's spread. The work, led by Adelaide University and the Olivia Newton-John Cancer Research Institute, was published on 21 August in EMBO Molecular Medicine.

The study found that patients with low levels of a molecule called miR-342, combined with high activity in the cancer-promoting E2F pathway, were more likely to develop metastatic disease. "When miR-342 levels fall, the E2F pathway becomes overactive, allowing dormant cancer cells that have already travelled through the body to grow into dangerous secondary tumours," said Associate Professor Philip Gregory of Adelaide University's Centre for Cancer Biology and SA Pathology.

In pre-clinical models, restoring miR-342 substantially reduced the spread of breast cancer to the lungs and bones. The researchers also tested palbociclib, a CDK4/6 inhibitor already used for advanced hormone receptor-positive breast cancer, and found that in models with low miR-342, the drug significantly reduced the growth of metastatic tumours even when given after the cancer had already spread. "CDK4/6 inhibitors are routinely used for patients with advanced hormone receptor-positive breast cancer, and our findings suggest they could also benefit a carefully selected group of patients with triple-negative disease," Gregory said.

Professor Robin Anderson of the Olivia Newton-John Cancer Research Institute said most breast cancer deaths occur because the disease spreads rather than from the primary tumour itself, and that triple-negative breast cancer's diversity has made it especially hard to develop targeted treatments. The researchers plan to confirm their findings in patient-derived pre-clinical models before pursuing clinical trials.

Triple-negative breast cancer accounts for about 10-15% of Australia's roughly 21,000 annual breast cancer diagnoses, but a disproportionate share of deaths because it is aggressive and can spread rapidly to distant organs.