New treatment for advanced ER+ breast cancer shows promise

A new proof-of-principle laboratory study has shown promising results for the treatment of oestrogen receptor positive (ER+) breast cancers that are resistant to current approaches, providing support for a potential new clinical trial. The study was conducted by Australian researchers and has been published in the journal Breast Cancer Research.

The standard of care for advanced ER+ breast cancer is a combination of hormone therapy and CDK4/6 inhibitors, but researchers are also investigating alternatives for patients whose cancer is not controlled by this treatment. In looking for new therapeutic targets, the study team focused on MDM2, a regulatory protein that controls the tumour suppressor protein p53. Described by some 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 and spread, the researchers investigated whether blocking MDM2, and thereby reactivating p53, could effectively target breast cancer. Using an MDM2 inhibitor that is currently in clinical trials for the treatment of leukaemia, the team assessed whether this approach could stop the growth of tumours in experimental models when used in combination with currently used hormone therapies or CDK4/6 inhibitors.

The researchers discovered that the MDM2 inhibitor together with either hormone therapy or CDK4/6 inhibitors was able to significantly reduce the growth of cancer cells in tissue culture and in mice. Furthermore, the researchers tested the treatment combinations in breast cancer models that had already become resistant to hormone therapy or CDK4/6 inhibitors and demonstrated that this new strategy is effective even in this setting.

“These are promising new results that may provide a new treatment pathway and be applicable to four in five patients with advanced ER+ breast cancer,” said Associate Professor Elgene Lim from the Garvan Institute of Medical Research.

“Our next step is to conduct a small-scale clinical trial to test the new approach in patients with advanced breast cancer.”

The project received discretionary funding of $91,600 over two years from Breast Cancer Trials (BCT), which supports researchers in developing collaborative, high-quality research projects and clinical trials that aim to find new and better treatments and prevention strategies for breast cancer. One-off grants of up to $50,000 per year over 1–2 years are available and applications can be submitted at any time.

Image credit: ©stock.adobe.com/au/Africa Studio

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