A new targeted therapy to make Triple-Negative Breast Cancers sensitive to hormone therapy

Project Description: Triple-negative breast cancer (TNBC) tumours lack three targets that are known to fuel breast cancer growth – estrogen, progesterone and HER2 receptors. This means that treatment against these targets, successful in other breast cancer types, are not effective against TNBC. This project aims to explore a novel approach, called targeted antibody therapy, to convert estrogen insensitive tumours, like TNBCs, into one that has the estrogen receptor, ultimately making these tumours responsive to available and effective hormone therapy. 

Why This Work is Needed: TNBC accounts for 15-20% of all breast cancers diagnosed. It has the one of the highest rates of recurrence, limited treatment options and with the poorest rates of survival. TNBCs are often treated with surgery and chemotherapy, and while initially effective, TNBC tumours treated with this therapy often recur and become resistant to treatment. Hence, new, and effective therapies for TNBC are desperately needed. 

Expected Outcomes: The findings from this study will reveal how and when to employ targeted antibody therapy that reactivates the estrogen receptor in combination with current standard of care therapies. If successful, this may generate additional treatment options for TNBC patients that will ultimately improve their outcomes. 

Project Details

TNBC is resistant to hormone therapies due to the lack of estrogen, progesterone and HER2 receptors. In most cases, TNBC is treated initially with surgery and chemotherapy, and while initially responsive, many patients develop recurrent and resistant disease. In addition, some chemotherapy regimens can have significant side effects, reducing the quality of life for these patients. Unfortunately, for those patients who do not respond to this surgery and chemotherapy, the average survival duration is only around 12 months. 

Antibodies are naturally created by the immune system to fight viruses, bacterial infections or cancer. The use of antibody therapies, where a protein is generated in the laboratory against a target protein, is an approach to combat cancer called targeted therapy.  

This project, led by Professor Andrew Scott from the Olivia Newton-John Cancer Research Institute, will investigate how effective an antibody called 6B3 is at treating TNBC. In mouse models, the team has shown that the 6B3 antibody can restore the expression of estrogen receptors to the tumour, hence making the cancer sensitive to anti-estrogen therapy. 

In addition, the team will use an imaging technique, PET/MRI to assess the response of cancer cells to 6B3 and determine the best timing for combination with anti-estrogen therapy. If successful, this non-invasive technique could be used to monitor the response of this novel combination therapy in patients.