New Research May Improve Treatments for Advanced ER+ Breast Cancer

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 new standard of care for advanced ER+ breast cancer is a combination of hormone therapy and CDK4/6 inhibitors and researchers are working to stay one step ahead of cancer, by investigating an alternative for patients whose cancer is not controlled by this treatment.

In looking for new therapeutic targets, researchers focused on MDM2, a regulatory protein that controls the tumour suppressor protein 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 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 leukemia, 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. Further, 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.

The project received discretionary funding from Breast Cancer Trials (BCT) of $43,200 in year 1 and $48,400 in year 2, which was awarded to Associate Professor Elgene Lim from the Garvan Institute of Medical Research.

A/Prof Lim is the Study Chair of the PATINA clinical trial, a member of the BCT Scientific Advisory Committee and heads the Connie Johnson Breast Cancer Research Lab at the Garvan Institute.

“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 Lim.

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

BCT 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. Discretionary funding grants are available to BCT members to support small scale research projects such as: pilot studies for proposed BCT trials; sub-studies of existing research protocols; small-scale translational research studies; and projects related to research methodology.

One-off grants of up to $50,000 per year over 1-2 years are available and applications can be submitted at any time by completing a Concept Proposal Form. This funding is available thanks to the generosity of BCT supporters.

For more information about Discretionary Funding and support for BCT members, please visit Research & Funding on our website here.

A copy of the study publication is available here:

MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer

Published: 12 August 2020

Breast Cancer Trials has been conducting clinical trials research for more than 40 years and the results have improved the treatment of the disease, changed clinical practice and saved lives through research collaboration. The research program brings together almost 800 researchers in 107 institutions throughout Australia and New Zealand. More than 16,000 people have participated in BCT clinical trials.

Media Contact: Anna Fitzgerald 0400 304 224 or anna.fitzgerald@bctrials.org.au

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