The Breast Cancer Research Unit (BCRU) at the Basil Hetzel Institute for Translational Health Research is focused on the development, progression and metastatic spread of breast cancer. Much breast cancer research is focused on the primary tumour in the breast, however what causes patient mortality most of the time is metastases; when the cancer spreads into other organs. Over 75% of patients with advanced stage breast cancer will have developed metastases into the skeleton, causing significant pain and side effects such as hypercalcaemia and fractures. Once the cancer reaches this stage chances of successful treatment are much slimmer. The BCRU, led by Michell McGrath Breast Cancer Fellow Professor Andreas Evdokiou, aims to identify therapies that will be effective in the breast as well as metastatic sites such as the bone.
Hormonal Breast Cancer Treatments
You may or may not be aware that estrogen can play a role in causing breast cancer. Estrogen is a steroid (a type of hormone) that is necessary for the normal development and growth of breasts and the organs important for childbearing. On its own in the breast, estrogen cannot do its job; it needs receptors (estrogen receptor alpha and estrogen receptor beta), to receive signals, which allow it to do things like stimulate breast cell growth and development.
Because estrogen and estrogen receptor alpha also support the growth of some breast cancer tumours, estrogen receptor alpha has been a target for current hormonal breast cancer therapies such as Tamoxifen for quite a long time. While it is an effective treatment for women with estrogen positive disease, many women unfortunately relapse while being treated.
It is not understood precisely why this relapse occurs. Currently, researchers do not have a clear picture as to how all the steroid receptors in the breast, including progesterone receptor (PGR) and androgren receptor (AR), communicate with each other. This may be why many women are relapsing from therapies which target the estrogen receptor; the treatments aren’t correctly developed to take into account the communication between all of the steroid receptors.
Researchers are investigating how all three receptors interact with each other in the breast cancer cells to produce an integrated response which will provide knowledge to assist the diagnosis of women more accurately and the potential diversification of treatment options.
The Immune System
Immune cells could not only be the key to breast cancer prevention, but also provide a basis for potential treatments. Everyone has T-cells to fight for their immune system and a rare population of those cells are known as gamma delta T-cells.
When there is cancer present these cells will move around targeting cancer cells and killing them before they have the ability to grow into tumours. However, of the millions of T-cells in our bodies, only 1-5 per cent are the cancer fighting gamma delta T-cells.
Researchers are using patients’ blood in vitro and increasing the numbers of the rare cells into millions, which could be successful at killing breast cancer either in the breast or breast cancer that has metastasised into the bone, once they are introduced into a patient.
Researchers say that this work is novel and unique with the potential to be translated into the clinical setting in a short time.
Cancer Tumour Hypoxia
Tumour hypoxia (lack of oxygen) is a major cause of cancer treatment failure for a wide variety of cancers. Within most solid tumours there are significant areas of hypoxia which contain cancer cells that no longer respond to conventional treatments such as chemotherapy and radiotherapy. This can lead to reappearance of the tumour and metastasis (spread of the tumour into the skeleton or other organs in the body).
A project in the BCRU is looking at the anti-cancer potential of a new class of drugs that can kill cancer cells present in hypoxic areas of a tumour. Conventional chemotherapies have harmful effects on bone health and many cancer patients who have and continue to receive certain chemotherapy are at a higher risk of developing osteoporosis due to the associated toxicities to cells of the bone and bone marrow.
The BCRU’s strategy is to maximise the effectiveness of therapy targeted to the hypoxic tumour while reducing toxicity to help improve understanding of these promising agents on bone cancer development, progression and metastatic spread of breast cancer.
It is hoped that this study will demonstrate the usefulness of this approach in treating bone cancers, eventually providing a new and more promising treatment option for breast cancer sufferers, as well as other forms of cancer.