Improving treatment for Poor-Prognosis Estrogen Receptor Positive Breast Cancers

Project Description: Endocrine therapy is an effective first-line treatment for many estrogen receptor-positive (ER+) breast cancers. However, some women are at risk of late relapse, highlighting the need to further optimise treatment for a subset of ER+ breast cancers. This new NBCF-funded study, led by Professor Christina Mitchell from Monash University, will help identify ER+ breast cancers at risk of poor treatment outcomes and develop new treatments for this subset of breast cancers. 

Why This Work is Needed: A proportion of ER+ breast cancer patients treated with endocrine therapy experience relapse. Treatment of these recurrent cancers is clinically challenging and effective treatment options are currently limited. Therefore, there is an urgent need to further predict and identify the subset of ER+ breast cancers that may eventually recur. This study will help develop novel treatments for ER+ breast cancers with a poor prognosis, which may help improve patient outcomes.  

Expected Outcomes: The study will help to develop new, more effective treatment options for ER+ breast cancers that are less sensitive to standard treatment, which can help reduce death from breast cancer.  

Project Details 

Up to 80% of breast cancers are estrogen receptor positive (ER+). ER+ cancer is normally treated with endocrine (hormone) therapy, and although this therapy has high initial success rates, a proportion of women with ER+ breast cancer will eventually relapse. Therefore, there is an urgent need to further optimise treatment for this subset of ER+ breast cancers to improve patient outcomes.  

Prof Mitchell and her team have discovered a protein, called a phosphoinositide phosphatase, which is present at increased levels in approximately half of ER+ breast cancer patients. They have found that ER+ breast cancer patients with high levels of the phosphatase have a poorer prognosis, suggesting that better treatment may be needed in this patient subgroup to improve their health outcomes. 

In addition, the team’s previous work in breast cancer cells suggests that using a drug that specifically targets the protein pathway that the phosphatase is active in may improve treatment response. To investigate this further, the team will use “organoids”, which are laboratory-grown three-dimensional tissues. The organoids in this study are cultivated from patient tumour samples, and they are a cutting-edge method for testing new precision treatments. 

This grant will allow researchers to learn more about the role the phosphatase and related proteins play in ER+ breast cancer. Using organoids, researchers will compare ER+ breast cancers with high and normal levels of the phosphatase protein. The team will also investigate whether the relative phosphatase levels could be a clinical measure to identify tumours that are less likely to respond to standard treatments. Finally, they will test whether blocking phosphatase-related signalling pathways could be an effective additional treatment for this subgroup of ER+ breast cancers.