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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.
The national breast screening program, by facilitating earlier detection, has contributed to a much improved survival rate for breast cancer. However, more advanced breast screening technology, such as 3D mammographic screening, could be available if there was evidence to support that they will further reduce deaths from breast cancer.
Professor Houssami has previously shown that 3D mammography has a 33 per cent higher detection rate than current mammographic screening technology. However, there is no evidence that the technology will reduce the risk of a woman developing breast cancer between screenings. This evidence is required before public health programs adopt 3D technology.
Although 3D mammograms are available in some private clinics in Australia, they are not backed by enough evidence to show that they provide better outcomes than standard screening.
Worldwide there are no public-funded screening programs routinely using 3D mammography, and this is because there is no evidence that it will have a true impact on the reduction of breast cancer deaths.
The evidence from this research project will prompt decisions on whether 3D mammography should be adopted as a primary screening strategy in Australia and globally sooner rather than later.
The main element of this multi-pronged research program aims to improve outcomes for Australian women, including those with dense breast tissue, by ensuring that 3D mammography evidence is available to inform on the most effective screening methods.
Professor Houssami’s program also aims to ensure every woman receives best-practice by contributing to developing international breast cancer surgery guidelines.
Recommendations from the research program will be integrated into guidelines and will be immediately available to clinicians, so they can provide the best informed and evidence-based surgical treatment to patients from the initial point of contact. These guidelines also aim to reduce unnecessary surgery for those with non-invasive breast cancers.
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.
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.
One fifth of breast cancers over-express a protein Her2, which promotes cancer. Although treatment of Her2+ breast cancers with Herceptin (Trastuzumab) is a key clinical milestone, many women develop Trastuzumab resistance and their cancers tend to return and spread to other parts of their bodies. Relapse is a major obstacle to effective treatment and patients’ long-term survival.
In a previous pilot study, Professor Ygal Haupt found that a cancer promoting protein, Mdmx, is highly expressed in breast cancers and could be responsible for getting in the way of a key suppressor of cancer, named p53. By targeting the protein Mdmx he was able to reduce the growth of luminal and triple negative breast cancers.
This new study expands the scope of investigation into Her2+ breast cancers. The results could define a new approach to treating the Her2+ breast cancer subtype, which has relied primarily on targeting the Her2 protein.
A number of Mdmx specific treatments are in clinical development, but not in the context of breast cancer. This study aims to establish the suitability of targeting Mdmx for treating Her2+ breast cancer and paves the way for clinical trials.
Professor Haupt believes the treatment will be suitable to most Her2+ patients. Trastuzumab responsive patients are likely to benefit from combined treatment of Trastuzumab and Mdmx targeting. Importantly, even patients with acquired resistance to Trastuzumab are predicted to benefit from an Mdmx inhibitory approach.
Those diagnosed with the aggressive HER2+ subtype of breast cancer are at high risk of developing secondary tumours (metastasis) in the brain.
Despite the introduction of HER2-targeted therapies for advanced breast cancer, the incidence of patients developing secondary brain cancer is increasing.
This has been attributed in part to improved control of the disease in other organs that extends the life of patients and to the lack of efficacy of HER2-targeting drugs against brain metastasis due to the development of resistance and/or limited drug permeability in the brain.
Currently it’s not possible to predict which patient will develop brain metastases, and there is no routine monitoring meaning patients are often diagnosed too late, when neurological symptoms are already apparent.
Once brain metastasis is detected, patients cannot be cured so there is an urgent need to identify biomarkers that can predict the development of brain metastasis and more effective therapies that would enable patients with HER2+ breast cancer at risk to be identified and treated earlier to improve clinical outcome.
Dr Normand Pouliot and his team will use a unique mouse model that closely mimics the spread of Her2 breast cancer to brain to identify new genes that cause brain metastasis and/or that predict breast cancer spread to brain.
They are seeking to identify a ‘gene signature’ specific to HER2+ brain metastasis which can be used to identify high risk patients prior to the development of brain lesions. These patients could then be closely monitored, allowing for earlier detection and more effective therapeutic interventions tailored to the individual patient.
They will also test novel combination therapies aimed at preventing the emergence of resistance to HER2-targeting drugs and improve their efficacy against HER2+ brain metastasis.
Mammography is the front line tool in breast cancer diagnosis and screening, however the technique, and the more recently introduced digital breast tomosynthesis (3D mammography), are limited in their ability to detect all tumours. They also use relatively high doses of radiation and require patients’ breasts to be uncomfortably compressed during the screening process.
This study is a continuation of research from a pilot study, in which Professor Brennan’s team, including Drs Tim Gureyev and Sheridan Mayo, developed an innovative alternative, called in-line phase-contrast computed tomography (PCT), a highly effective, low-dose, pain-free solution to future breast screening that will ultimately help to reduce deaths from breast cancer.
PCT produces large improvements in image quality, providing improved sensitivity and specificity of breast cancer diagnosis compared to existing mammographic techniques. It can detect very small tumours potentially without the need for compressing the breast, and could prevent false readings from breast screening.
This two-year project aims to provide a path for the clinical implementation PCT and outline how the new imaging technique should be used. This will include developing guidelines for how clinicians can quantify, evaluate and optimise the detection of small tumours in breast tissue using PCT, as well as identifying key imaging parameters and data analysis techniques.
The scope of the project includes conducting the world-first patient trial and via the NBCF-funded BREAST program, allowing expert radiologists in Australia and the US to assess images produced using PCT and compare them with images from currently available imaging technology.
Overall, the project will result in the establishment of a new technique and imaging protocol, transforming breast cancer diagnostic methods for the better.