Overcoming endocrine resistance in breast cancer

Background

Breast cancer is the most common cancer in Australian women, with one in seven developing the disease by the age of 75. Two thirds of breast cancers are estrogen receptor positive (ER+), which means the cancer cells are dependent on estrogen to grow and increase in number. Following surgical removal of ER+ breast cancer, patients are often treated with hormone therapy to block the effects of estrogen on any remaining cancer and reducing the risk of recurrence. If there is a recurrence (which can happen as many long as twenty years initial treatment) the cancer often appears in a distant site like bone are brain where it has become resistant to hormone therapy.

The research

In previous research, Professor Ormandy and his team found that a protein (called ELF5) is involved in breast cancer cells becoming resistant to hormone therapy. During hormone therapy, ELF5 levels increase and the breast cancer cells become dependent on ELF5 to grow and increase in number, rather than estrogen.

In this project, the team will continue their investigation of targeting ELF5 as a new treatment strategy to prevent hormone therapy resistance in patients with ER+ breast cancer.

In the laboratory, the researchers will test whether reducing ELF5 can prevent or reverse hormone therapy resistance, and whether ELF5 alone can cause or accelerate hormone therapy resistance. The results of this work will potentially enable the development of new drugs to interfere with ELF5.

Based on the finding that ELF5 levels rise during hormone therapy, the research team aims to establish a prognostic test to determine which patients will become resistant to hormone therapy and whether additional chemotherapy would be beneficial. No such test currently exists but could be easily implemented as a similar test is used to determine whether a breast cancer patient is ER+.

The researchers will also explore the use of the drug denosumab to stop ELF5 levels rising and therefore prevent resistance to hormone therapy. Denosumab is currently used to prevent bone loss in breast cancer patients. Repurposing a currently used drug is a fast way for a new treatment option to reach patients. The researchers anticipate the prognostic test they will establish could be used to predict whether denosumab in combination with hormone therapy is recommended.