Using hormone targeted drugs to switch on the immune response against metastatic breast cancer

Project Description: Estrogen receptor positive (ER+) breast cancer is the most commonly diagnosed breast cancer subtype and whilst some patients respond to endocrine therapies such as Tamoxifen, up to 30% of patients will develop tumours that are resistant to treatment and spread (metastasise), resulting in poor outcomes. The most common site of cancer spread after a diagnosis of ER+ breast cancer  is to the bone, a painful lesion occurring in  up to 70% of patients. A/Prof Belinda Parker and the team (Peter McCallum Cancer Centre) have discovered that endocrine therapies have varied impacts on the bone marrow immune cells that can influence the spread of cancer to bone. They have found that specific hormone therapies can activate bone immune cells, whilst increasing the cancer cell visibility to the immune system, arming the body to attack its own cancer before it begins to grow and spread in the bone. This study will use preclinical models of metastatic breast cancer to examine the effects of a range of standard-of-care, along with new and next line endocrine therapies on the immune system within metastatic sites such as the bone. This increased understanding may lead to new therapeutic combinations that alter the bone immune environment prior to the arrival of cancer cells to ensure that they can be destroyed before it is too late to intervene.

Why the Work is Needed: Breast cancer is the second leading cause of cancer-related deaths in Australia with most of these deaths due to the spread of the cancer to distant organs. Thus, there is an urgent need to develop new therapeutic approaches to prevent the initial spread of cancer.

Expected Outcomes: The successful outcomes of this study will uncover new therapeutic combinations with the potential to change the bone environment prior to the arrival of cancer cells to promote their destruction and prevent the cancer from spreading. This study will provide the rationale for future clinical trials to ultimately reduce the spread of aggressive ER+ breast cancer.

Project Details

Around 80% of breast cancers diagnosed in Australian women are estrogen receptor positive (ER+). While some patients respond to endocrine therapies such as Tamoxifen, up to 30% of patients will develop tumours that are resistant to treatment and spread (metastasise), often to bone, leading to severe morbidity and eventual mortality in most patients. The most common site for spread of these cancers is to the bone, a painful lesion occurring in up to 70% of patients with metastatic disease.

A/Prof Belinda Parker and the team from the Peter McCallum Cancer Centre have discovered that a major factor in spread and growth of breast cancer in the bone is changes that occur in the immune system within the bone environment. A/Prof Parker and colleagues believe that standard of care hormonal treatments alter the immune system in these distant sites so instead of fighting the tumour, the immune system supports the establishment and growth of breast cancers metastasis in the bone.

With this NBCF support, the team will use preclinical models of metastatic breast cancer to examine the effects of a range of standard-of-care and alternative endocrine therapies on the immune system within metastatic sites such as the bone. This increased understanding may lead to new therapeutic combinations that alter the bone immune environment prior to the arrival of cancer cells to ensure that they can be destroyed before it is too late to intervene.