Reprogramming the Estrogen Receptor to Improve Breast Cancer Treatment

Project Description: Women with estrogen receptor positive (ER+) breast cancer not only suffer from the side effects of anti-estrogenic drugs, but for many, these therapies are not curative and patients will often develop therapeutic resistance. This project will test a novel therapeutic approach to reprogram the estrogen receptor, instead of eliminating its activity, to effectively destroy the tumour.

Why This Work is Needed: Despite development of ever more potent anti-estrogenic drugs to treat ER+ breast cancers, this strategy does not cure patients, with 40% of women relapsing. At best, life is prolonged. In addition, many suffer from drug side effects, a critical issue since treatment lasts for 5-10 years. New, less toxic and more effective treatment strategies for ER+ breast cancer are a critical unmet need.

Expected Outcomes: This study will prove that reprograming the estrogen receptor can be an effective and durable therapy for ER+ breast cancer, especially for breast cancers that stop responding to standard-of-care treatments due to drug resistance and for which no other treatment options are available.

Project Details

Estrogen receptor positive breast cancer is the most common cause of breast cancer, affecting up to 80% of female and 90% of male breast cancer patients. In ER+ tumours, the hormone estrogen fuels the growth of the cancer. As such, current treatment options aim to either block the estrogen receptors, or lower the levels of the estrogen hormone in the body. This, in effect, starves the tumour of its fuel. However, this treatment also leads to estrogen deprivation in the rest of the body, which can lead to side effects.

This study, led by Dr Amy Dwyer from the University of Adelaide, will trial a completely new treatment strategy. Instead of eliminating estrogen receptor activity, the team will test therapies that reprogram the estrogen receptor to prevent the growth of tumours but retains activities needed by the body.

The project will trial drugs that are already on the market, which have been shown to modulate estrogen receptor activity. There will likely be additional benefits to these new treatments, including promotion of bone and muscle health, increased libido and prevention of hot flushes. The hope is that this new approach may be able to treat women with breast cancer, without making them feel miserable in the process.