A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,593,125.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 investigates anastrozole (Arimidex) as a preventative agent for women with moderate to increased risk of developing breast cancer. It is a multi-centre, randomised, double blind control trial which has the potential to benefit many millions of women worldwide. Anastrozole is an aromatase inhibitor (AI). AIs are a class of endocrine drug which have been shown to be at least as effective as tamoxifen but without the serious side effects seen with tamoxifen. Anastrozole has been shown to be 60% better than tamoxifen in preventing a second breast cancer in women already diagnosed with breast cancer. Women who participate in this study will be postmenopausal with a relative risk of at least two-fold of developing breast cancer. They will be randomised to receive either anastrozole or placebo as a daily tablet, and neither the woman nor her treating clinician will know which treatment has been allocated (double blind study). To investigate whether anastrozole effects bone density, a baseline bone density scan will be measured prior to study entry. This sub-study will investigate bone density in greater detail and the potential role of bone preserving treatment (bisphosphonate). The primary endpoint for the IBIS 2 study is the development of histologically confirmed breast cancer, invasive or non-invasive.Read moreRead less
IBIS II: A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,732,559.00
Summary
The IBIS II trial builds on the successful IBIS 1 breast cancer (BC) prevention trial in determining whether a chemopreventive strategy towards BC is beneficial. Women who are postmenopausal with an increased risk of BC are randomised to receive either anastrozole (an aromatase inhibitor) or placebo as a daily tablet. Neither the woman nor her clinician know which treatment has been allocated (double blind study). IBIS 2 has the potential to benefit many higher risk women worldwide.
Malaria is characterised by defective T cell responses, particularly suppressed T cell growth. T cells are critical to malaria protection and defective immune responses are likely to benefit the parasite. We want to find out how immune-responses are turned off in malaria, so that then we can do something about this, and help fight off the parasite. Malaria kills over 2 million children each year and there is no effective vaccine. We have two important clues as what may be happenning to cause sup ....Malaria is characterised by defective T cell responses, particularly suppressed T cell growth. T cells are critical to malaria protection and defective immune responses are likely to benefit the parasite. We want to find out how immune-responses are turned off in malaria, so that then we can do something about this, and help fight off the parasite. Malaria kills over 2 million children each year and there is no effective vaccine. We have two important clues as what may be happenning to cause suppressed T cell growth during malaria infection. Firstly, we found a massive increase in T cells expressing a surface molecule called CD38 duirng infection. Increases in these cells correlated with decreases in the ability of the T cells from the animals to grow. Indeed, other researchers had observed that in mice CD38 T cells can suppress immunity. Secondly, we hypothesized that they may be responsible for the impaired T cell reactivity observed during acute malaria, and the general poor state of immune responses in humans living in areas where they are being constantly infected by the parasite. Indeed, when we removed cells expressing CD38 from blood cells from such individuals, these 'recovered' and were able to grow much better in our assays. Therefore we propose that CD38 T cells are importnat mediators of malaria immuno-suppression. We now want to understand how the parasite induces these CD38 T cells, and how their ability to suppress T cell responses can benefit the parasite. Knowing this we aim to develop vaccines which can avoid being turned off by malaria. T cells expressing CD38 are also increased in cancer and acute viral disease, such as late stage HIV. Understanding their role in malaria will also give us new clues to fight such diseases.Read moreRead less
In Parkinson's disease only specific brain cells die, these cells are unusual in that they contain a dark coloured pigment called neuromelanin. The presence of this pigment is thought to play a role in the death of these cells. Evidence from many different diseases has demonstrated that a type of cell damage called oxidative damage is caused by an increase in tissue iron levels. Iron levels are increased in the brains of persons who have died with Parkinson's disease but only in the part of the ....In Parkinson's disease only specific brain cells die, these cells are unusual in that they contain a dark coloured pigment called neuromelanin. The presence of this pigment is thought to play a role in the death of these cells. Evidence from many different diseases has demonstrated that a type of cell damage called oxidative damage is caused by an increase in tissue iron levels. Iron levels are increased in the brains of persons who have died with Parkinson's disease but only in the part of the brain which contains neuromelanin. This increase in iron is thought to lead to oxidative damage and thus cell death in Parkinson's disease. Why iron should be increased specifically in this part of the brain is unknown but it has been shown that neuromelanin binds tissue iron and that the interaction between iron and neuromelanin can result in tissue damage. These events are suggested to underlie the specific vulnerability of the neuromelanin-containing cells in Parkinson's disease. However as yet very little is known about this pigment or how it interacts with iron. This research investigates neuromelanin in the normal brain and in the brain of persons who have died with Parkinson's disease. The project aims to demonstrate how neuromelanin interacts with iron and how neuromelanin, both in the presence and absence of iron, can influence oxidative cell damage. The use of human neuromelanin makes this research unique and it will provide important and novel information regarding the role of this pigment in the aetiology of this devastating disease.Read moreRead less
Predicting The Individual Risk Of Prostate Cancer In Australian Men
Funder
National Health and Medical Research Council
Funding Amount
$348,656.00
Summary
Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently a ....Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently available for prostate cancer. We will apply standard statistical methods to existing data from the Australian Risk Factors for Prostate Cancer study and from the Australian Institute of Health and Welfare to develop a prostate cancer risk prediction model. We will test how factor like age, detailed family history, diet, baldness status and possibly previous PSA tests and prostate biopsies predict the risk. After developing the model, we will test the accuracy of the predictions in three ways. First, using existing data from the Australian Prostate Cancer Family Study, we will see whether the number of cases in a group of men is close to the number predicted by the model (calibration). Second, to test whether the model discriminate well men who develop prostate cancer from those who do not, we will collect family trees in a sample from the Melbourne Collaborative Cohort Study. We will use these data also to estimate the optimal cut point: men above this level of risk will be considered at high risk. Third, we will apply the model to existing data from the Dutch Prostate Cancer Family Study (DPCFS) to test whether the optimal cut point identify high-risk men and to validate the model in a non-Australian population. Finally, we will prepare a computer package that health professionals will use as decision-making tool in different scenarios including individual cancer risk assessment, design of prevention trials and targeting prevention programs to high-risk men.Read moreRead less
Genetic Epidemiology Of Endometrial Cancer: Towards Understanding Aetiology And Improving Risk Prediction.
Funder
National Health and Medical Research Council
Funding Amount
$353,573.00
Summary
Studies investigating thousands of genetic markers have revolutionised our understanding of genes involved in cancer, and shown that a single gene can be associated with multiple cancers. We will conduct the largest ever study to find new genes for endometrial cancer, the most common gynaecological cancer. Our unique approach will examine >11million markers across the genome, some specifically in regions known to be important for other cancers. Findings will be used for risk prediction models ....Studies investigating thousands of genetic markers have revolutionised our understanding of genes involved in cancer, and shown that a single gene can be associated with multiple cancers. We will conduct the largest ever study to find new genes for endometrial cancer, the most common gynaecological cancer. Our unique approach will examine >11million markers across the genome, some specifically in regions known to be important for other cancers. Findings will be used for risk prediction models.Read moreRead less
Clinical, Environmental And Genetic Factors And The Risk Of Oesophageal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$145,685.00
Summary
Oesophageal cancer is a rapidly fatal disease which is becoming more common in Australia, the United States and other industrialised nations. This study will examine the mechanisms leading to the development of oesophageal cancer and aims to measure the effects of genes and environment on the burden of cancer. Ultimately, this research will help target persons at highest risk so that screening, prevention and surveillance efforts can be directed more effectively.
Modelling Of Clinic And Ambulatory Blood Pressure On Cardiovascular Risk And Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$133,957.00
Summary
Whilst ambulatory blood pressure monitoring data has been shown to be a good predictor of cardiovascular events, there remains controversy as to its utility in clinical practice. This project will use data from existing population and clinical cohort studies to examine the role of ambulatory blood pressure in risk assessment and hypertension management in Australia and around the globe. The findings are likely to have a major impact on clinical guidelines for hypertension management.
Intelligent Total Body Scanner For Early Detection Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$499,963.00
Summary
Melanoma is the 4th most common cancer in Australia; the main screening tool is a time-consuming total body examination with a hand-held dermoscope. This project aims to develop a total body scanner using fast-refocusing lenses to take total body dermoscopy images of all skin lesions in approximately 6 minutes, integrated with a computer aided diagnostic tool providing a risk score for each lesion incorporating medical history, genotypic and phenotypic risk markers.