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Approximately 70 per cent of women diagnosed with breast cancer have at least one other chronic condition, and one third have three or more.
The presence of chronic conditions (such as diabetes, cardiovascular disease, kidney disease and musculoskeletal disease) impacts treatment choices, increases treatment toxicity, is associated with reduced adherence to treatment and overall survival.
The prevalence of chronic conditions in breast cancer survivors is higher than aged matched cancer-free population, suggesting that either cancer itself or its treatment predisposes patients to chronic conditions. Despite these statistics, the management of chronic conditions is poorly integrated into the care of breast cancer.
The study aims to measure the burden of chronic conditions in breast cancer patients and survivors in Australia and identify populations most at risk of chronic conditions before and after breast cancer.
It will also examine mechanisms behind the development of chronic conditions and consider ways in which they could be prevented.
Professor Bogda Koczwara will develop and pilot strategies for better integrated management of chronic conditions in breast cancer that will lead to improved outcomes (particularly in bone and heart health) and to serve as a model of care for other cancers.
Understanding the origin of chronic conditions in breast cancer and the mechanism for their development may offer insight into prevention of not just chronic conditions but cancer itself.
Breast cancer is a complex disease that changes over time by acquiring several genetic defects, or mutations. There are multiple mutations that need to occur in order for breast cancer to develop, grow quickly or spread around the body.
This study aims to identify the factors that make early benign breast tumours become the fast-growing malignant disease known as cancer. Additionally the project supports the idea that long term remission and breast cancer cure can be achieved by adopting a personalised medicine, where treatments are directed to the specific core components of a cancer.
We know breast cancer is not one disease, but has many different sub-types, and that breast cancer learns how to escape treatments by changing over time. Because of this, it has become clear that no single treatment will ever be able to cure all types of breast cancer.
However, with a deeper understanding of the biological markers (genes) that make up the core components of each type of cancer, personalised therapies can become more refined and effective.
Dr Antonella Papa will investigate two specific genes that frequently mutate in ER+ and HER2+ breast cancer subtypes and result in the proteins PI3K and PTEN being made.
In normal tissue, PTEN, a key tumour suppressor, controls the activity of PI3K which keeps pro-growth factors in check. In cancer, the two proteins behave quite differently; PI3K is super-active and PTEN becomes inactive or is lost. The lack of PTEN activity is commonly associated with poor prognosis in many tumour types and with patients developing resistance to targeted therapies (i.e. HER2+ breast cancers).
The study will investigate how the presence of these mutated proteins affect breast tissue biology in mice to identify the pro-growth factors that accumulate over time and make the tumour bigger and more aggressive.
By identifying these new factors, Dr Papa and her team will be able to address why current treatments are only partially effective in treating advanced breast cancer and will test whether targeting these newly identified pro-growth factors can be used to develop more effective therapies for breast cancer linked to PI3K and PTEN mutations.
The findings of this study have the potential to influence treatment decisions for the large number of patients with advanced breast cancer.
Chimeric antigen receptor (CAR) T cell therapy is a novel form of immunotherapy where white blood cells are transferred to the patient to boost the immune system. It has recently had remarkable effects in patients with cancers of the blood, such as leukaemia; however, the success against solid cancers has been modest.
In particular, advanced breast cancer has large solid tumours that have spread to other organs of the body, which are very difficult to treat with current therapies.
Dr Clare Slaney and her team have made a breakthrough in a new treatment for breast cancer that can eradicate large tumours in mice, which has not been possible before. Preliminary research data also demonstrates that following the initial treatment the immune system develops a memory response able to fight recurring tumours.
This exciting new approach involves a transfusion of white blood cells plus an injection of a vaccine. The white blood cells are genetically modified to attack breast cancer cells, and the vaccine is made up of a virus that also has the power to attack cancer cells.
In this project, Dr Slaney will seek to more fully understand how the combined treatment works, and test the treatment against tumours that have spread to other organs. She believes that once administered, the treatment could potentially remain effective even after the primary tumour is eradicated, eliminating any remnant or newly arising tumour cells. This is particularly important, as the threat of breast cancer recurrence in other organs is a constant worry for patients.
This study will serve as preparation for a clinical trial in cancer patients, which could be ready in 5-10 years. If successful, it would represent the most effective new breast cancer therapy known and could have a significant impact for reducing breast cancer mortality.
Triple-negative breast cancer accounts for approximately 15 per cent of all breast cancers, and they are challenging to treat because they are typically more aggressive and donâ€™t respond to current treatments.
Much of the underlying biology that increases cancer risk is unknown and as such, reliable biomarkers that would help with diagnosing early stage, high risk triple-negative breast cancer patients have not yet been identified.
One key factor in the fast progression of triple-negative breast cancer is a high level of vascularisation â€“ when the tumour develops blood vessels such as capillaries and veins. This vascularisation process is a precursor to the tumour spreading to other parts of the body (metastasises).
New promising treatment methods are arising that focus on targeting the vascularisation process for many types of breast cancer, however, it is still poorly understood for triple-negative breast cancer. A better understanding of the biological mechanisms involved could result in potential prognostic markers or new therapies for breast cancer patients.
The process for testing our understanding of how cells interact is to culture them in a petri dish. However, experiments on cells in petri dishes do not accurately mimic the natural human tissue environment and cannot represent the progression of breast cancer in the human body.
In order for researchers to obtain useful results from laboratory cell culturing, they need to be able to replicate the breast environment as closely as possible.Â In this project, to properly understand the cellular interactions in triple-negative breast cancer that control its vascularisation and metastasis, Dr Laura Bray and her team aim to upgrade the existing practice in culturing tumour cells by developing a more sophisticated, three dimensional culture technology to create experimental models that better reflect real breast cancer interactions, and have greater clinical relevance.
The study will also seek to identify key biomarkers that can predict the response to breast cancer therapy, and develop a model system to test patient biopsies which would help determine if the patient’s cancer is likely or unlikely to develop into metastatic form of triple negative breast cancer, and to individualise their treatment program.
Two thirds of the Australian female population are overweight or obese which increases their risk of developing hormone receptor-positive breast cancer after menopause.
The hormone estrogen plays a pivotal role as, in addition to being produced by the ovaries, it is also produced by fat and the majority of obesity-related breast cancers are estrogen-dependent.
Dr Kristy Brownâ€™s research program is wide-ranging in its scope and intends to provide better understanding of the regulation of metabolic pathways in cells of the breast with the aim of identifying new therapy options for the effective treatment and prevention of breast cancer.
She is continuing with research that demonstrated a direct metabolic link between obesity and breast cancer and expanding this research to look at the possible interaction between breast inflammation, the metabolism of cells within the breast and the production of estrogen that drives tumour growth.
Additionally, this program will look further into an appetite stimulating proteinÂ produced by the gut, called ghrelin, and its potential to inhibit the bodyâ€™s ability to synthesise estrogen and the growth of breast tumours, including breast cancers with limited available treatments.
Overall this program will take the next steps in building on previous research into new ways of blocking cancers spreading to other sites, provide hope for treating women with limited options, and look at treatments that have fewer side-effects.
We have known for over 300 years that childbearing protects against breast cancer, but the reasons are not clear.
A woman’s reproductive history is a strong risk factor for breast cancer; women who do not bear children or who have them at an older age are at an increased risk of developing the disease. This is alarming given the global reproductive trend of women bearing fewer children. Societal changes have meant that the age at which women are having their first baby is also increasing.
Itâ€™s not possible to dictate when women should have children just to decrease their breast cancer risk, but there is potential to develop therapies aimed to mirror this protection if we understand how pregnancies protect the breast against cancer development.
Currently Tamoxifen is the most frequently prescribed treatment for the treatment of existing breast cancers and has resulted in a 50 per cent fall in the death of breast cancer patients in the last 30 years. Tamoxifen is also used in the preventative setting as it can reduce the risk of estrogen positive benign and invasive breast cancers in high risk women (those with a family history).
However, Tamoxifen has numerous toxicities, including increased risk of thromboembolism, endometrial cancer, hot flushes and vaginal symptoms. It has a low compliance rate, with only 50 per cent of patients adhering by the full treatment, meaning preventative strategies with fewer side effects are needed.
Dr Kara Britt believes that a protein that is increased in the breast tissue of individuals who have borne children may be responsible for the protective effects of pregnancy and childbearing.
The study will focus on testing whether this protein, when given to mice, can inhibit breast cancer development, or slow the growth of tumours. This will allow Dr Britt and her team to determine if it should be considered for clinical use as a preventative for high risk women.
Australian women who have been identified with a high-risk of breast cancer often donâ€™t undergo recommended cancer prevention and screening procedures.
This study will use interviews and surveys to study women enrolled in the kConFab (Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer) Follow-Up Study to determine why; from the perspectives of high-risk women and their clinicians.
High-risk women include those who have the BRCA1 and BRCA2 gene mutation, either themselves or in their family, or have a strong family history of breast and/or ovarian cancers.
The range of potential options available to manage cancer risk includes intensified screening such as MRI scans, tablet medications that reduce cancer risk, and surgery such as preventive mastectomies.
Professor Phillips believes reasons for the limited take up of these options could include concerns about side effects, lack of knowledge about available options by both women and their doctors, and perhaps difficulty accessing the full range of options, particularly for women in rural and regional Australia.
However, the study is also expected to discover important barriers to uptake that have not previously been considered.
She says there is an urgent need to more fully understand why high-risk women do not take steps to reduce their chance of developing breast cancer. This information will inform the development of educational materials and changes to health policy that will reduce the national cancer burden by helping women get the best care.
The incidence of breast cancer has historically been lower in Asian countries, but this is changing rapidly with economic development. It is changing more rapidly for Asian women living in developed countries.
We know this because the Multi Ethnic Cohort Study of the Japanese community living in Hawaii has shown that exposure to Western lifestyles had a substantial impact on breast cancer risk. Their breast cancer incidence has increased enormously in the last 50 years and is now at the same level as for the Caucasian population, especially for third and fourth generations of Japanese Americans.
Australia has a growing population of women and families of Vietnamese descent and, given global trends, their incidence of breast cancer is likely to increase rapidly in the next few generations.
This presents not only a major challenge for breast cancer control in Australia, but also an opportunity to study the causes of breast cancer, and in particular, to try to prevent an increase in this disease Â Australiaâ€™s Vietnamese community. If we can do this, it would have profound implications for the enormous populations of Asian women living in developing and developed countries across the world.
The objective of this study is to establish a cohort of women and families of Vietnamese descent who have been living in Australia for different amounts of time to study the impact environmental factors, such as migration and acculturation, have on risk of developing breast cancer.
This project has the potential to put in place an early warning system and educational program about breast cancer and how to reduce risk and develop opportunities for early detection in this expanding migrant community.
The ovarian hormones, estrogen and progesterone, are critical in normal development of the breast, but are also major drivers of breast cancer risk although the precise details of how remains unclear.
Cancer can be viewed as abnormal development in which regular developmental mechanisms have gone awry. To prevent cancer, a key approach is to define these normal mechanisms and determine how they are corrupted during early cancer formation.
In this project Dr Heidi Hilton will document cell types in the normal breast across the whole of reproductive life, and by identifying the impact of hormones on these cell types, she aims to draw a link between hormone exposure, the presence of hormone receptors for estrogen (ER) and progesterone (PR), and the switching on/off of cellular pathways that may be harmful to these cells. This is important, as the detection of ER and PR in new breast cancers is crucial to decisions about treating these cancers.
Dr Hiltonâ€™s recent data shows that ER and PR are found in different cells in the normal breast, but can also be found in cells, called progenitors, that are thought to be susceptible to the first cancer-causing activity. She and her team have shown that progesterone stimulates these progenitor cells to grow and is associated with cancer-stimulating properties.
This project will build on this knowledge and take a new approach to understanding how hormones (particularly progesterone) influence breast cancer risk, by identifying the targets of these hormones in normal breast and pre-invasive cancers (called ductal carcinoma in situ).
Although the hormones progesterone and estrogen are critical in normal breast development, women taking hormone replacement therapy (HRT) that contains synthetic progesterone analogues, called progestins, have an increased breast cancer risk.
The outcome of this study could lead to earlier diagnosis for breast cancer, and also help women who are faced with the difficult decision of deciding between using HRT, or dealing with the uncomfortable and often debilitating symptoms of menopause.
Our DNA is like a blueprint of biological guidelines for staying alive and functional, but itâ€™s up to RNA to carry out these guidelines, and many RNAs play crucial, active roles in the cell.
Some RNA molecules are involved in switching genes on and off, and others called non-coding RNA are not involved in gene changes but can have other important roles. The number of non-coding RNAs in the human genome is unknown and not much is known about many of them.
Professor Gregory Goodall recently identified an abundant form of non-coding RNA, called Circular RNAs (CircRNA), which are likely to be regulators of cell activities associated with cancer invasion and metastasis â€“ i.e. they could play a role in cancer development and progression.
Following on from that initial surprising discovery, he is now conducting one of the first investigations into the role of this novel type of regulatory molecule in breast or any other cancer.
The aim of the study is to substantiate evidence regarding the role of these circular RNA molecules in affecting cancer cell properties, in particular how they influence cancers to progress to an invasive, metastasising form.
This is a new exciting avenue of research that in the long run could lead to discovery of new types of therapeutic target or a diagnostic marker for early stages of metastasis.
More immediately, Professor Goodall hopes his results will stimulate other researchers to join the investigation of cancer roles of these molecules.