Prevention research only makes up about 4% of the global financial commitment to the breast cancer fight, and considering breast cancer is the most common cancer found in women, there is very limited knowledge about how to prevent it.
The Breast Biology & Cancer Unit at the Basil Hetzel Institute for Translational Health Research are investigating why the breast is so susceptible to cancer, not in terms of lifestyle factors, but the actual underlying cellular mechanisms that underpin breast cancer susceptibility. This team is led by Associate Professor Wendy Ingman.
The team has a number of focus areas:
The Immune System
Understanding the role our immune cells play in the risk of developing breast cancer has taken a big step forward. Research into the immune cells, known as macrophages, has shown the cells’ role changes in response to the hormone fluctuations that occur each month.
The team’s study found that the cells play a role in the normal function of the breast but at certain stages in a woman’s menstrual cycle they may actually help to make the breast more susceptible to cancer. The BBCU now believe there is a ‘window of risk’ which opens when a woman has a period and the levels of the hormone progesterone drops. Immune defences in the breast tissue are down at this time and women could be more susceptible to the initiating factors that lead to breast cancer.
It has been known for some time that there is a link between the number of years of menstrual cycling a woman has and breast cancer risk. Research undertaken in the BBCU is now uncovering the cell-to-cell interactions that impact this risk.
By increasing their knowledge of the biological factors that underpin breast cancer susceptibility, the team are hopeful they might one day be able to close these windows of risk, and reduce women’s lifetime risk of breast cancer.
The BBCU are now working to unravel the mechanisms that are responsible for the increased risk and taking steps to alter them.
Mammographic Density (MD) is the density of a women’s breast tissue, and women with high MD have a 4-6 times increased risk of developing breast cancer, a relative risk that is substantially larger than any other risk factor for breast cancer. This is including the more commonly known BRCA carrier status, which comparatively is responsible for significantly fewer breast cancer cases; an estimated 2-5%.
1 in 3 breast cancers can be explained by Mammographic Density.
Little is known about what causes high breast density and its increased risk of breast cancer, but a link has been found between high collagen content, which is a structural component of the breast, and high breast density. Fibroblasts are the main type of cells that produce collagen; so it is likely that fibroblasts play a role in breast cancer risk.
The BBCU are investigating how fibroblasts differ in function from high density to low density breast tissue when stimulated with TGFB and Estrogen; two key reagents which are also found within the breast. When extracting fibroblasts the team found that there were specific genes which showcased different patterns of expression depending on whether they were from high density or low density breast tissue.
With further research into these very early findings, it is possible that in the future, this could form the basis of identifying a possible therapy to decrease breast density tissue in women who have high density breasts, and therefore lower breast cancer risk.
There is a risk factor for breast cancer which is related to the Transforming Growth Factor Beta (TGFB) 1 gene (which exists in the mammary gland) and is a multifunctional cytokine, which regulates cell division, cell death and the immune system.
Much research on this particular gene has concentrated on its direct effects on the cells that actually form the tumours. It’s a gene which is always there being expressed, but women have different levels of expression depending on the particular genetics, and genetics is what causes increased breast cancer risk.
The BBCU has been investigating the effects on cells surrounding the tumours, believing those cells support the tumour development. They have found the TGFB gene not only affects the cells that form tumours, but also surrounding cells called macrophages.
The research shows a bigger picture of how the gene works. They believe macrophages affect the risk of tumour formation in the breast and need more research.
Studies began in 2010 and continue, having identified how it works in vivo, the team will now study how the gene affects human tissue. The BBCU will also conduct in vivo studies looking at interactions between the TGFB gene and tumour formation.
This work could lead to the development of a strategy to reduce a woman’s breast cancer risk.
Spinal Cord Memory
The BBCU is investigating how spinal cord memories during pregnancy can affect the risk of breast cancer.
The changes in the spinal cord during pregnancy are like “memories”, and these memories could in turn affect breast cells and the risk of developing cancer.
This project was developed after the BBCU found evidence while conducting another study. They’re working with Neuroimmunologist, Dr Mark Hutchinson from the Physiology Department at Adelaide University to continue the work.
This research could lead to a new prevention target; the opportunity to treat women for something that makes their bodies change in the way that a pregnancy does and therefore reduce their risk for their lifetime.
In order to achieve this, researchers need more information about the cells and their mechanisms and the research is ongoing.
The project is also being supported by the National Breast Cancer Foundation.
Establishing a Breast Tissue Bank
A unique resource for breast cancer prevention research is being created, which has the potential to accelerate research findings and help understand the cellular mechanisms that underpin breast cancer risk.
It is a challenge to construct a living tissue bank, but the BBCU are determined to build a bank that will continue to provide information over the next 20 or so years.
In traditional tissue banks, the tissue is preserved in a special fixative – it can be used for certain types of experiments but there are always limitations. The BBCU are collecting fresh tissue that allows researchers to do much more; study the biology and look at the different cell types within the tissue. The team can isolate the different cell types that are inside the breast tissue and prepare them in a special way that means they can be stored frozen in liquid nitrogen. The cells and tissue can then essentially be ‘brought back to life’ as needed.
Having ready access to the tissue would give breast cancer researchers the chance to complete work in six months that might previously have taken them up to five years.
The BBCU is seeking tissue from women who are having elective breast surgery, for example breast reduction surgery where tissue would normally be discarded. They are also gathering unaffected tissue from women who are having cancer related surgery. Educating both clinical and surgical staff, as well as recruiting women prior to their surgery, has been quite an undertaking for the research team. They are now expanding the program into more facilities including private hospitals.