Reversing treatment resistance in ER+ breast cancer

Lead Researcher: Dr Joanna Achinger-Kawecka

Institution: Garvan Institute of Medical Research

Cancer Council NSW Funding: $434,310

Funding Duration: 2020 – 2022

Background

Breast cancer is the most common cancer in Australian women, with around 20,000 women expected to be diagnosed during 2020. 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 (endocrine therapies such Tamoxifen) to block the effects of estrogen on any remaining cancer and reducing the risk of recurrence. However, around 30% of women treated with these therapies develop endocrine resistance and do not respond to the treatment. Alternative treatments for women with endocrine resistance are very limited, leaving women at higher risk of cancer relapse. More research is urgently needed to better understand how endocrine resistance develops so new treatments can be found.

The Research

New research suggests that endocrine resistance may be caused when cancer goes through a series of genetic changes (mutations of the DNA) or epigenetic changes (changes to the chemical make up or 3-D structure of DNA). Dr Joanna Achinger-Kawecka and her team recently discovered a pattern of epigenetic changes to the 3-D structure of the DNA that are fundamental to the development of endocrine resistance. In this project, Dr Achinger-Kawecka will study this pattern of DNA changes further, detailing the mechanisms that lead to endocrine resistance. They’ll also test currently available drugs that target epigenetic changes to see if they can reverse the development of endocrine resistance and restore sensitivity to treatment.

Impact

By improving understanding of the mechanisms that lead to endocrine resistance, the team hope to identify new treatment strategies for women with ER+ breast cancer who develop resistance to treatment. Their findings may also have implications for other hormone-dependent cancers such as prostate, ovarian and endometrial.