Stopping breast cancer treatment resistance and relapse

Susan Clark

Professor Susan Clark

Garvan Institute of Medical ResearchFunding duration: 2016 - 2018

This project has worked to improve treatments and reduce the major challenge of some breast cancer patients’ resistance to endocrine therapy and relapse. 


In Australia, breast cancer will affect 1 in 8 women by the time they are 85. About 70% of breast cancers are what is known as estrogen-receptor (ESR1) positive. The majority of women with this type of breast cancer will have endocrine therapy at some stage during their treatment. Endocrine therapy reduces the risk of breast cancer recurring. However, about a third of patients develop resistance to this therapy and relapse within 15 years of first receiving treatment.

In a previous study, Professor Clark and her team identified changes in the chemical modifications of DNA of ESR1 positive breast cancers that cause them to be resistant to endocrine therapy.

The research

In this project, the team has been investigating the DNA chemical or epigenetic changes further. The new data they have gathered about endocrine resistant breast cancer will enable the researchers to develop biomarkers to identify which patients are at high risk of relapse.

Professor Clark and her team have also been investigating ways of reversing the epigenetic DNA changes to restore treatment sensitivity. They have discovered that a drug called Decitabine, commonly used to treat blood born cancers, can reverse the epigenetic changes and stop the growth of tumours. Their laboratory testing will determine if this drug also has the ability to restore sensitivity to endocrine therapy. Their hope is to show that Decitabine in combination with endocrine therapy could be an effective treatment approach for relapsed breast cancer.

The impact

Endocrine resistant cancer currently represents the most significant challenge in breast cancer treatment. This research has significantly improved knowledge of how and why endocrine resistance occurs, and importantly, how to identify those at highest risk. The findings point to a promising new treatment approach for patients who currently have limited options.

Lead ResearcherResearch Team

Professor Susan Clark
Garvan Institute of Medical Research

Dr Clare Stirzaker
Professor Christopher Ormandy
Associate Professor Elgene Lim

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