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Over time, breast cancers that have spread to other parts of the body (also called advanced or metastatic cancer) become resistant to current treatments and these patients have a very poor prognosis.
With the response rate to first line treatments (such as chemotherapy) for advanced breast cancer between 30–70 per cent, and the disease-free period often only 7–10 months, discovering new therapeutic targets and drugs for advanced breast cancer treatment is crucial.
Multi-drug resistance in breast cancer is linked to the drug-resistance protein, P-glycoprotein, which is associated with disease relapse and death.
Professor Des Richardson and his team aim to target this protein with a new drug. They have recently developed an innovative strategy where novel compounds hijack a tumour’s cell drug-resistance machinery (P-glycoprotein) to trick and kill drug-resistant cancer cells.
The aim of the study is to develop and test the chemical make-up of the new drug to overcome tumour resistance so it is effective in treating advanced breast cancer.
They will establish biomarkers (blood test) to gauge whether the treatment is working, and determine the appropriate dosage, so it can be fast-tracked for clinical trials and be available for use in the next few years.
For breast cancer to grow and spread, that the tumour needs a blood supply to provide oxygen and nutrients – the process of developing veins and capillaries in the tumour is called vascularisation.
The tumour can develop a blood supply by two main methods: by promoting the growth from existing blood vessels into the tumour; or by the cancer cells themselves forming vessel-like structures for blood to flow through – a process called ‘vasculogenic mimicry’.
Highly vascularised breast cancer tumours, such as invasive ductal carcinoma, are able to grow aggressively. Current treatments designed to inhibit blood supply to the tumours are not effective and the prognosis is poor.
Associate Professor Claudine Bonder and her team have previously shown that vascularisation in healthy tissues is supported by an individual protein called interleukin-3 (IL-3), and they believe this protein could also play an important role in the vascularisation and growth of aggressive breast cancers.
This study aims to demonstrate that IL-3 contributes to the initial growth of breast tumours and is an important common factor for both methods of tumour vascularisation and thus breast cancer metastasis (when the tumours spread to other parts of the body).
A/Prof Bonder believes that by targeting IL-3 with a blocking antibody (which is currently in clinical trials for acute myeloid leukaemia patients) could be repurposed and rapidly developed for better management for breast cancer patients – particularly for those with the aggressive and difficult to manage invasive ductal carcinoma breast cancers.
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.
Women living with advanced breast cancer (also referred to as metastatic cancer, when the tumour has spread) have many points of contact with the health system during their heavy treatment schedule.
Although the general level of cancer care continues to improve, advanced breast cancer patients have indicated that a more tailored system is needed, because they feel their individual physical and emotional needs are not being met, which impacts their quality of life and health outcomes.
For example, having a single contact at their treating centre or hospital, fears about the cancer spreading and having enough information to know how to help themselves are among some of the needs and concerns for women living with advanced stages of breast cancer feel are lacking in current treatment programs.
However, despite growing awareness of these unmet needs, there doesn’t appear to be a move toward developing a tailored supportive care program that these women can access to address their many and changing needs and concerns.
This study sets out to develop and trial a supportive care program that is based on patient input.
It will bring together advanced breast cancer patients, breast cancer oncologists, cancer nurses, allied health professionals, palliative care physicians, breast cancer advocacy and support organisations, cancer researchers and IT expertise to develop a support program that can be accessed either as a face-to-face resource, online or via a smartphone app.
In addition to consumer informed content, the modules will draw together evidence-based resources to inform symptom self-management; healthy lifestyle behaviours; strategies to minimise worry and anxiety; how to recognise and where to get help for depression; practical issues (financial support, superannuation and wills); and issues of relevance for women living with advanced breast cancer, including bone health, menopausal symptoms, diet and exercise.
The program will draw together in one place, for the first time, resources developed specifically for women with advanced breast cancer by key groups such as BCNA, BreaCan and Cancer Council Victoria.
Rural breast cancer patients who undergo surgery to remove breast tumours commonly report practical and financial barriers to accessing face-to-face care in regional and metropolitan centres.
Given increasing access to high speed internet across Australia, online oncology support models have the potential to address the psychosocial, financial and practical burdens experienced by rural breast cancer patients.
By providing web-based pre-operative information to guide expectations for surgical procedures and outcomes, and post-operative follow-up appointments delivered by video-conference, clinicians may be able to reduce rural breast cancer patients’ anxiety, improve their quality of life, and lead to reduced costs imposed on the patient and health care system.
This project will gather high level evidence about the psychosocial and economic impacts of online oncology support via a randomised controlled trial. The trial aims to compare the outcomes for women on the trial to those receiving usual care in the following areas: 7-day post-operative anxiety; 45-days post-operative health-related quality of life; 45-days post-operative health sector perspective cost-effectiveness.
The aim is to provide reliable information to guide expectations for surgical procedures and outcomes, as well as reduce breast cancer patients’ anxiety, length of hospital stay, pain and other post-operative complications. Additionally, it will provide information about the effectiveness and cost-effectiveness of an online oncology support model for rural breast cancer patients.
Bone is the most common location that breast cancer spreads to (metastasises), and is found in 80 per cent of breast cancer patients with the advanced stage of disease. Once breast cancer spreads to bone, it is incurable as there are no effective treatments currently available.
Breast cancer in its advanced stage often spreads to the spine and pelvis, resulting in pain and stiffness that leads women to avoid physical activity which reduces their overall health.
However, exercise has been shown to provide wide-ranging health benefits to cancer patients, such as survival, quality of life, and reduced bone pain; therefore strategies to promote safe and effective delivery of exercise to women with advanced breast cancer and bone metastasis is very important.
Initial exercise is believed to have an anti-cancer effect, slowing tumour growth by changing tumour biology, as well as an ability to increase blood-flow to tumour sites which helps make other therapies, such as chemotherapy, more effective.
Professor Robert Newton and his team will deliver safe and effective exercise programs using resistance and aerobic exercise to women with advanced breast cancer over 12 weeks to investigate reductions in tumour growth, improved quality of life, better physical function in muscle and bone, and healthier heart and lungs.
The aim is that the program would become immediately available and implemented for all advanced breast cancer patients in Australia.
Recent studies have found that premenopausal women with high-risk, estrogen-receptor positive early breast cancer who were given a combination of ovarian suppression and aromatase inhibition treatments to deprive the body of estrogen (rather than tamoxifen which is current standard treatment) had improved outcomes.
In older, postmenopausal women, treatments that include aromatase inhibitors can cause bone loss, which leads to loss of strength and a higher likelihood of fractures.
Given that estrogen deprivation with ovarian suppression and aromatase inhibition is a relatively new treatment for younger, premenopausal women, there is limited information on how it will affect their bones.
Dr Sabashini Ramchand will conduct a double-blind randomised controlled study to quantify the effect of ovarian suppression and aromatase inhibition on bone loss, and determine whether denosumab (a common treatment given to older women for osteoporosis) is effective in preventing this bone loss.
Dr Ramchand will also aim to identify markers that will help to predict which women will be at particularly high risk of bone loss, and examine the effect of estrogen depletion on cardiovascular risk markers (body fat distribution, diabetes and cholesterol levels) and on quality of life.
This study is expected to have an immediate impact on the clinical care of younger breast cancer survivors by providing them and their medical team with a clearer understanding of the risk-benefit ratio of estrogen depletion. This project will provide the foundation for enhancing the treatment and quality of life for young survivors of breast cancer.
The discovery of BRCA1 and BRCA2, genes that predispose family members to a high risk of developing breast cancer was an important break-through in breast cancer research.
It is now understood that these genes account for only two per cent of all breast cancer cases and the genetic cause of the majority of familial breast cancer remains unknown.
Prof Campbell has identified 40 genes for which there is evidence that they could also be responsible for a genetic predisposition to breast cancer.
Until recently, the identification of new breast cancer genes would have been of limited use due to the time and cost of genetic testing, but the advent of advanced gene sequencing technologies has now made it possible for entire panels of genes to be screened at a fraction of the time and cost of the traditional testing methods used for breast cancer genes BRCA1 and BRCA2 alone.
Consequently, in this project Prof Campbell will sequence his 40 genes across a large international cohort of 5,000 familial breast cancer cases (who have tested negative for the BRCA genes), and 5,000 control cases, including Australian women, to identify new genes responsible for familial breast cancers.
Identifying the genetic causes for familial breast cancer can provide significant opportunities for primary and secondary prevention of breast cancer, as well as improving risk assessment, genetic counselling and management for individuals in high-risk breast cancer families.