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Millions of women with a type of breast cancer fuelled by the female hormone estrogen have benefited from treatments such as tamoxifen and femara, which in most cases successfully prevent breast cancer returning later in life.

However, a third of these hormone-driven breast cancers develop resistance to preventative treatments and the cancer becomes metastatic, spreading throughout the body.

Treatment resistance is the highest cause of mortality in breast cancer. It’s vitally important to prevent this metastatic stage of breast cancer but as yet there are no effective tests or personalised therapies that can identify or help these women and men.

Dr Liz Caldon

Dr Liz Caldon

NBCF-funded Dr Liz Caldon believes that the survival and quality of life would improve significantly if it was possible to predict from the first diagnosed cancer whether it is likely that someone’s cancer will recur, and then treat any recurrence with drugs that are specifically toxic to hormone resistant breast cancer.

But first she is focusing on improving our understanding of hormone resistant breast cancer, specifically the molecular changes that occur as the cancer cells develop resistance, including which genes might be involved.

With this knowledge she and her team will design better predictive tests that detect the presence of resistant cancer cells well before they start to grow as a secondary cancer. They will also determine if these cells have any particular qualities that mean they could be specifically targeted and destroyed during therapy.

Ultimately, this research project aims to eliminate the development of resistance to treatment and stop recurrence from ever happening, providing hope for women and men with hormone resistant breast cancer.

Thanks to medical research it’s now widely recognised that harnessing the immune system is a powerful way to target and kill cancer.

Patients with high levels of immune cells within their tumour respond better to both standard therapies (radiotherapy and chemotherapy) and therapies designed to enhance the immune response against cancer (immunotherapy). However, many patients don’t have immune cells in their tumours so these treatments are not very effective, and more research is needed.

One potential strategy for these patients is the use of white blood cells which are genetically engineered to eradicate cancer cells. These cells, called ‘chimeric antigen receptor T cells’ (CAR T cells), are very effective in blood cancers but don’t work well in other cancers including breast cancer.

One reason for this is because cancer produces adenosine, a substance which has a powerful ability to suppress the immune system. It creates an environment designed to switch off immune cells, giving the cancer plenty of opportunity to grow unchecked.

Dr Paul Beavis

Dr Paul Beavis

In a four-year NBCF-funded study, Dr Paul Beavis aims to reprogram the CAR T cells to block the effects of adenosine, so the immune system can recognise, find and destroy any cancer in the body.

The adenosine pathway is most relevant in triple negative breast cancer which is the most aggressive and hardest to treat subtype. Development of a successful immunotherapy would be a significant breakthrough and would have a huge impact on the lives of women diagnosed the disease, and particularly for those with triple negative breast cancer.

Of the more than 16,000 Australian women diagnosed with breast cancer each year about 15 per cent, 2400 women, have a sub-type of the disease called triple negative breast cancer.

Women with triple-negative breast cancer have less treatment options and poor outcomes compared to women with other type of breast cancer, so there is an urgent need to improve treatment methods.

Chemotherapy is a component of treatment for many types of breast cancer, but it is the only effective treatment for triple negative breast cancer. It is a powerful tool; however it has undesirable side effects and can become less effective over time if tumours develop resistance, causing patients to relapse even if their initial treatment was effective.

Many chemotherapy drugs work by damaging the DNA of the cancer’s cells. Some tumours can reverse the effect of the treatment by repairing the damage and continuing to divide and grow.

Professor Robert Baxter

Professor Robert Baxter

A promising approach to treating drug resistance is to prevent the cancer cells from repairing the damage caused by the drug. Professor Rob Baxter and his team have discovered a previously unknown way in which triple-negative breast cancer cells can repair DNA that has been damaged by chemotherapy.

The aim of this project is to learn more about this process and discover how to prevent it. Ultimately, the aim is to develop a new treatment that would allow chemotherapy to work more effectively, improving survival for many women with triple negative breast cancer.

Triple negative breast cancer is more aggressive than other breast cancer subtypes and is more likely to spread to other parts of the body faster. It is also the most difficult type of breast cancer to treat.

Once the cancer spreads – a process called metastasis – the survival outlook falls dramatically, but at present, doctors have no way to predict which patients’ breast cancer will metastasise.

Many triple negative breast cancers have high levels of two particular proteins which are known to promote the spread of cancer cells. This NBCF-funded study aims to determine if extremely high levels of these proteins can be used to identify the patients whose disease is more likely to spread.

Dr Normand Pouliot

Dr Normand Pouliot

A second focus of the study is to test a new strategy for treating triple negative breast cancer. Unlike other subtypes of breast cancer, there are no therapies specifically tailored for triple negative. Chemotherapy is the only treatment option and it is not very effective once the cancer has spread.

Dr Normand Pouliot aims to see if standard treatments that are being successfully used for other types of breast cancer (such as tamoxifen) can be made to work against triple negative as well.

He will test if blocking the two proteins found in triple negative with novel inhibitors, allows standard treatments to work and stop the growth of the cancer cells.

The combined approach of this project could point to early indicators and more effective treatment of patients with aggressive triple negative breast cancer – two potential breakthroughs that could save the lives of many women in future.

Research has improved the success rate of breast cancer to 90 per cent, but for women with metastatic breast cancer (when the cancer has spread beyond the breast) modern treatments are only able to prolong life, not stop the cancer progressing.

Targeted therapies are a new class of medicines that have improved the survival and quality of life of breast cancer patients. Targeted therapies are among the last treatment options for metastatic breast cancer patients in the very advanced stages of the disease, and while some patients experience substantial benefit from these medicines, unfortunately, many others either do not respond or experience severe toxicity.

Dr Ashley HopkinsIn this project, Dr Ashley Hopkins will use advanced mathematical techniques aiming to identify predictors of good and bad outcomes to targeted therapies used
in metastatic breast cancer. Dr Hopkins will analyse data that has been collected across a series of clinical trials on targeted therapies to determine who responded well and why, so these drugs can be more accurately prescribed.

Dr Hopkins intends to share the study results so that clinicians and breast cancer patients can assess the benefit and risks of these treatments – such as the likelihood of a positive outcome weighed up against the drugs toxicity.

This type of information can help guide treatment decisions that may improve response rates and decrease toxicity to specific therapies, provide an indicator of when to use alternate therapies or focus on palliative care, which may also lengthen the survival of cancer sufferers.

If the success rates of targeted therapies can be improved, they could be included as options in standard care within the next 10 years, helping to successfully treat women with metastatic breast cancer.

Olaparib is known to be effective treatment for breast and ovarian cancers in people with inherited mutations. Many more patients do not have a genetic risk but have cancers arising from spontaneous mutations. Our clinical trial aims to find out whether olaparib benefits patients with breast or ovarian cancers with non-inherited mutations or abnormalities.

Altered metabolism is a key feature of cancer, with metabolic pathways reprogramed to meet the energy demands of cancer cell growth. However, little is known about the role of increased lipid metabolism in breast cancer. We now show that ACC1, a key regulator of lipid metabolism, is expressed by breast tumours, and that inhibiting ACC1 impairs breast cancer progression. This proposal will validate and characterise ACC1 as a novel therapeutic target for the treatment of breast cancer.

Determine the effects of exercise alone +/- systemic therapy on tumour response, metabolic effects, tumour transcriptome and circulating biomarkers in ER+ve and ER-ve PDX models. Determine the effects of exercise on immunological and metabolic responses, cytokines, tumour vascular density and circulating biomarkers in immunocompetent (MMTV-PyMT) mouse tumour models. To determine the feasibility of a graded exercise program in patients with early breast cancer during the administration of adjuvant chemotherapy or ET.

Women with metastatic breast cancer are dying from the disease because no treatments have yet been developed that can stop tumour growth once it spreads beyond the breast.

The standard treatments currently available for women with metastatic breast cancer can prolong life, but ultimately do not prevent death. These treatments include toxic chemotherapy which, although initially effective at killing cancer cells, simultaneously attacks some healthy cells and causes unpleasant side effects.

Dr Kylie Wagstaff

Dr Kylie Wagstaff

In this four-year NBCF-funded study, Dr Kylie Wagstaff is aiming to find a specific biomarker that differentiates healthy cells from cancer cells. This discovery could firstly lead to easier and more accurate detection of metastatic breast cancer and, secondly, aid the development of drugs that recognise and target only cancer cells.

The new treatment would be much more effective, while also significantly reducing the harmful side effects women experience as a result of standard breast cancer care. This much-needed improvement in treatment for women with metastatic breast cancer could mean better prognosis and greatly enhanced quality of life during treatment.

The main cause of death from breast cancer is when it spreads to other parts of the body such as the brain, bones and liver. This metastatic stage of the disease can be treated to prolong life, but as yet no treatments are curative.

An exciting emerging area of research called immunotherapy may have the answer. Immunotherapy works by making the cancer visible to the body’s immune system so it can seek out and destroy cancer cells. Promising results have already been seen in metastatic melanoma, however to date immunotherapies have had limited success treating breast cancer patients.

Dr Simon Junankar

Dr Simon Junankar

NBCF-funded Dr Simon Junankar and his team are seeking to understand the one of the fundamental questions in cancer – how cancer cells avoid detection by the body’s immune system. They believe this knowledge could provide an explanation for why immunotherapy for breast cancer is not yet successful.

The researchers will use a cutting-edge DNA barcoding technique that tracks individual cancer cells through the body to the organ in which they settle. They are looking to see if the cancer cell will create a metastatic tumour, how the cancer cells respond to immunotherapy, and specifically if they are resistant to immunotherapy.

This DNA barcoding technique can determine if the cancer cells were resistant to therapy from the beginning or if the therapy prompts the development of resistance. This information will help determine the best combinations of immunotherapies for effectively treating metastatic breast cancer and eliminating cancer cells from the body.

Activating the patient’s own immune system early could ultimately prevent metastatic disease developing, dramatically reducing deaths from breast cancer.

The study is focused on two common subtypes of breast cancer which means the findings will be applicable to the majority of breast cancer patients. If successful, the study paves the way for breast cancer immunotherapy clinical trials in the not too distant future.