Targeting a new ‘hidden’ aggressive subtype of estrogen receptor positive breast cancer

Project Description: Around 70% of breast cancers express the estrogen receptor (ER) and can be treated effectively with anti-estrogen therapy. Unfortunately, around 20% of these breast cancers are more aggressive and resistant to this type of hormonal therapy, which leads to an increased risk of relapse and poorer outcomes for these patients. A/Prof Pilar Blancafort, from the University of Western Australia has discovered that a gene called AAMDC could be used as a biomarker for this very aggressive and previously ‘hidden’ subtype of estrogen receptor positive breast cancer. The aim of this project is to develop clinically useful tests for the detection of AAMDC in human estrogen receptor positive breast cancer samples and to understand the role AAMDC plays in these tumours, which may lead to development of novel drugs to treat this aggressive subtype of breast cancer.   

Why This Work is Needed: For the 20% of patients with anti-estrogen resistant breast cancer and the poorest outcomes, new treatments are desperately needed. It is therefore important to be able to identify those who may not respond to anti-estrogen treatments and provide them new therapeutic options personalised to their tumour to improve the prognosis and outcomes for these patients.   

Expected Outcomes: This project aims to develop clinically useful tests to detect the ‘hidden’ aggressive subtypes of estrogen receptor positive breast cancer marked by elevated levels of the gene AAMDC. The project will also increase our understanding of why AAMDC helps breast cancer cells develop resistance to anti-estrogen therapy. This information may lead to the development of new drugs that can disable AAMDC and improve response to anti-estrogen therapies.  

Project Details  

70% of all breast cancers are fuelled by estrogen, meaning that anti-estrogen therapies are a very effective treatment option to control the disease. Whilst these drugs work very well in most patients, up to 20% of patients have estrogen receptor positive breast cancers that are resistant to this treatment. These patients have an aggressive form of ER+ breast cancer, which claims the lives of around 1,000 women per year in Australia. 

Currently, there are limited options to predict which patients have the aggressive subtype, and which does not respond to anti-estrogen therapy leading to an increased risk of relapse and poorer outcomes. For patients with this aggressive subtype, there are limited targeted treatment options. 

A/Prof Pilar Blancafort, from the University of Western Australia, has recently discovered a new gene, which could allow both detection and treatment of these breast cancer cases. The gene, called AAMDC (Adipogenesis Associated Mth938 Domain Containing), helps cancer cells to survive when treated with anti-estrogen therapy. 

This project will develop clinical tests for the AAMDC gene, which allows clinicians to identify which patients will do poorly under anti-estrogen treatment. The team will also increase the understanding of this gene and how it protects estrogen receptor positive breast cancers from anti-estrogen therapy which may lead to the development of novel treatments that target the AAMDC gene and its pathways.