Understanding how Estrogen Receptor Positive (ER+) breast cancers evade the immune system

Project description

Estrogen Receptor Positive (ER+) breast cancer is the most prevalent subtype, representing approximately 70% of all breast cancer cases. Endocrine therapy is the standard treatment to prevent recurrence, significantly reducing mortality in people with early-stage disease. However, 30% to 50% of people experience relapse, often occurring late—from five to over ten years after the initial diagnosis. These late recurrent cancers are challenging to predict and resistant to existing therapies. Immunotherapies that activate the person’s own immune system to kill cancer cells have revolutionised the treatment of other cancers. However, ER+ breast cancers evade the immune system by unknown mechanisms and immunotherapies are currently ineffective. Improving understanding of how ER+ breast cancers escape from immune surveillance is essential for the design of new treatments.

PIK3CA is the most frequently mutated cancer-causing gene in ER+ breast cancer, which promotes tumour growth and therapy resistance. Previous research by Professor Christina Mitchell from Monash University and the team have discovered elevated levels of a phosphoinositide (PI)-phosphatase in about 46% of ER+ breast cancers and associated with poor prognosis. The team also showed that PIK3CA and the PI phosphatase act together and contribute to ER+ breast cancer evasion of the immune system.

In this NBCF-funded study the team aims to understand how a PIK3CA-PI phosphatase axis helps ER+ breast cancers escape immune detection and how immune recognition of tumour cells can be reactivated.

Why is this work needed

While most people with ER+ breast cancer respond well to endocrine therapy, the risk of relapse is a continual threat, which can lead to metastatic disease—the principal cause of breast cancer-related mortality. Immunotherapy has shown encouraging results in treating certain cancers, including Triple Negative Breast Cancer. However, ER+ breast cancers manage to evade the immune system through mechanisms that remain unclear, making current immunotherapies largely ineffective. Gaining a deeper understanding of how ER+ breast cancers escape immune surveillance is crucial for the development of effective new treatment strategies.

Expected outcomes

Successful outcomes of this study will uncover the role of the PIK3CA-PI-phosphatase pathway in enabling ER+ breast cancers to evade immune detection and reveal strategies to reactivate the immune system to improve outcomes for people with relapsed ER+ disease.