Stopping breast cancer treatment resistance and relapse

Garvan Institute of Medical Research 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

Background

In Australia, breast cancer will affect 1 in 7 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 cancer cells that cause them to be resistant to endocrine therapy.

The research

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

Professor Clark and her team also investigated ways of reversing the epigenetic DNA changes to restore treatment sensitivity. They discovered that a drug called Decitabine, commonly used to treat blood born cancers, can partially reverse the epigenetic changes and stop the growth of tumours in pre-clinical models. Their laboratory testing in a small study has shown promising results that using the drug in combination with endocrine therapy can restore the sensitivity of the tumour cells in pre-clinical models to this treatment.

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 can occur, and importantly, provides a new approach to potentially identify those at highest risk. This exciting discovery provides a promising new treatment approach for patients who currently have limited options.

Professor Susan Clark and her team plan to further validate the new treatment regime in pre-clinical models and to utilise these findings to create a future diagnostic test that could be used to monitor treatment response in women during endocrine therapy.