Scientists Identify Molecule Driving Breast Cancer Spread

Triple-negative breast cancer (TNBC) is responsible for some of the poorest outcomes related to breast cancer treatment. Because TNBC lacks the hormone receptors and HER2 proteins targeted by many existing breast cancer therapies, it has historically been more challenging to treat. 

However, a joint study by researchers at Adelaide University and the Olivia Newton-John Cancer Research Institute has uncovered a potential path to tackling one of the most aggressive forms of breast cancer, raising hopes for more effective treatments to stop the disease from spreading.

The research found that patients with low levels of a naturally occurring molecule called miR-342 and higher activity in a cancer-driving pathway known as E2F were more likely to develop metastatic disease.

In laboratory models, the researchers found that restoring miR-342 levels significantly reduced the spread of breast cancer to other parts of the body, including the lungs and bones.

The team also found that palbociclib, an existing breast cancer drug known as a CDK4/6 inhibitor, reduced the growth of metastatic tumours in models with low levels of miR-342. Palbociclib is currently used to treat advanced hormone receptor-positive breast cancer.

Repurposing existing treatments

The findings could potentially open a new use for Pfizer's Ibrance (palbociclib), an established breast cancer treatment, in a molecularly defined subset of patients with triple-negative breast cancer. 

Associate Professor Philip Gregory of Adelaide University, co-senior author of the study, says the findings could help identify patients most likely to benefit from CDK4/6 inhibitors and inform future clinical trials.

He explains: “Palbociclib and other CDK4/6 inhibitors are currently being evaluated in triple negative breast cancer, but responses have been variable. Our findings suggest that specific subgroups of these cancers may be particularly sensitive to CDK4/6 inhibition and, with further validation, could potentially help identify patients most likely to benefit and inform future clinical trials.”

The researchers found that giving palbociclib after cancer cells had already spread could be particularly effective at stopping tiny metastatic tumours from developing further. 

Co-senior author of the study, Professor Robin Anderson, from the Olivia Newton-John Cancer Research Institute, says: "Rather than shrinking the primary tumour, this treatment may prove most valuable by stopping tiny metastatic deposits from developing into life-threatening secondary cancers.

"Our study identifies a distinct subgroup of patients whose cancers share a common biological weakness, opening the door to a much more personalised treatment approach."

Stopping the spread

According to the US National Cancer Institute, five-year relative survival is around 91% for patients whose disease remains localised, but falls to just 12% when the cancer has metastasised to distant parts of the body.

"Primary tumours can often be treated successfully with surgery or local therapies, but once cancer spreads throughout the body it becomes far more difficult to control," Robin continues. 

Triple-negative breast cancer accounts for around 10–15% of Australia’s approximately 21,000 breast cancer diagnoses each year but causes a disproportionate number of breast cancer deaths because of its aggressive nature and tendency to spread rapidly to distant organs. 

Philip echoed these sentiments regarding the importance of ensuring cancer remains localised. He says: “A major goal of cancer treatment is to prevent the development of metastatic disease, as once cancer has spread, it becomes much more difficult to treat.”

Key company – Pfizer

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CEO: Dr Albert Bourla, Chairman and CEO

Pfizer developed and markets Ibrance (palbociclib), an oral CDK4/6 inhibitor that targets proteins involved in regulating cancer cell growth. 

Ibrance is approved for treating hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, with the drug also receiving a US approval in 2026 for a regimen in HR-positive, HER2-positive metastatic disease. 

The Adelaide research raises the possibility of using palbociclib in a molecularly defined subset of patients with triple-negative breast cancer, subject to further validation and clinical trials.