Study guides next generation of advanced breast cancer therapy

A new study from scientists at the Garvan Institute of Medical Research has uncovered a possible treatment regime for women with treatment-resistant oestrogen receptor positive (ER+) breast cancer. ER+ tumours account for approximately 70% of breast cancer cases, and unfortunately around one third of them will develop resistance to the standard hormone therapies.

The new study, led by NBCF-funded researchers Associate Professor Elgene Lim, Dr Heloisa Milioli and Dr Neil Portman, investigated ways to increase the activity of a tumour-suppression protein called p53. Referred to as the ‘gatekeeper of the genome’, p53 helps protect DNA from the damage that leads to cancer. As all tumours have to inactivate p53 to grow, the researchers investigated methods of increasing the action of p53 to prevent cancer spread.

They discovered that if they suppressed a regulatory protein called MDM2, using a drug that is currently in clinical trials for leukemia, they could improve p53 activity. A combination of the MDM2 inhibitor together with either  currently used hormone therapies or CDK4/6 inhibitors (palbociclib or ribociclib) led to a significant decrease in cancer growth, in both cells in culture and tumours in mice. These combination therapies also resulted in decreased growth of breast cancer cells that had become resistant to the standard treatment regime.

“This study has shown us a promising new path for advanced breast cancer, which we think may be applicable to as many as four in five patients with advanced ER+ breast cancers. We hope this new approach will help us stay one step ahead of breast cancer drug resistance,” said Dr Portman.

NBCF-funded researcher Dr Neil Portman. Photo James Horan.

The team is now working towards a clinical trial at the St Vincent Hospital in Sydney, to test whether this combination therapy is effective in people with advanced ER+ breast cancer.

“This study is another demonstration of how research underpins new cancer therapies,” said A/Prof Lim. “Our hope is to translate these findings into clinical trials, and ultimately make an impact on patient outcomes.”

NBCF-funded researcher Associate Professor Elgene Lim. Photo James Horan.

This research was supported by the National Breast Cancer Foundation, Love Your Sister, The Estate of the late RT Hall, the Cancer Institute of New South Wales, Breast Cancer Trials and Novartis Australia, and was published in the prestigious open-access journal Breast Cancer Research.

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