New Targeted Therapy for Late Recurring Breast Cancer

Project Description: Patients with estrogen receptor positive (ER+) breast cancer are treated with standard-of-care endocrine therapy to prevent recurrence. However, 35% of patients treated with endocrine therapy have late recurrences (cancer returning after 5 years or more). At present, these patients have generally poor outcomes. This new NBCF-funded study, led by Dr Liz Caldon from the Garvan Institute of Medical Research, will investigate a new targeted drug therapy for late recurring breast cancer. 

Why This Work is Needed: Approximately 1 in 4 breast cancer deaths occur in patients who have had endocrine therapy and recur more than 5 years after their first diagnosis. At this time, there are no predictive tests for late recurrence and no targeted therapies for these patients.  

Expected Outcomes: This preclinical study will investigate the potential of a previously approved oral drug to treat late recurring breast cancer. This means that, if the study shows that it is effective, it may be rapidly introduced as an inexpensive and safe treatment option with minimal side-effects for those with late recurring breast cancer, which will help improve their treatment outcomes.  

Project Details 

Patients with estrogen receptor positive (ER+) breast cancer are treated with standard-of-care endocrine therapy to prevent recurrence. However, a proportion of these patients will have late recurrences (breast cancer returning more than 5 years after the initial diagnosis). Late recurring breast cancer is a priority for research, as there are no effective tests to predict recurrence, no targeted therapies for this disease, and disease prognosis is generally poor. 

Preliminary data from Dr Caldon and her team suggest that a major cause of late recurrence is “endocrine tolerance”. This means that some cancer cells are able to survive the initial hormone therapy, and then grow and spread once therapy has ceased.  

The team has identified that these aggressive cancers are vulnerable to a class of drugs called Rac inhibitors. In this study, they will determine the best way to use Rac inhibitor drugs to stop the growth and spread of recurrent breast cancer. They will monitor the effect of the drug on individual cancer cells in mouse models using world-class imaging technology. 

In addition, the team has identified a protein, called P-Rex1, which is a potential marker of poor prognosis and late recurrence in ER+ breast cancers. In this study, the researchers will use state-of-the-art preclinical models of late recurring breast cancer to determine whether P-Rex 1 can be used to identify patients who will respond to Rac inhibitor therapy.  

The study ultimately aims to help develop a new therapy to prevent and treat late recurrence in breast cancer, which will help improve patient outcomes and reduce breast cancer related deaths.