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Many breast cancer patients need to take chemotherapy drugs for a long period of time, such as tamoxifen which is usually prescribed for five years.

To achieve the best results from chemotherapy it’s necessary to correctly balance the level of the drug in the body by changing the dose on later cycles. Patients need sufficiently high enough doses to kill their breast cancer cells but not too high that they are unable to cope with the harsh side-effects.

However, each person will take to chemotherapy differently based on factors such as body size, age, other drugs and foods they are taking and how hard their kidney and liver work hard to flush foreign toxins. Current standard practice for measuring the correct dose doesn’t take all these factors into account, resulting in imprecise dosing for individual patients. Some may receive doses of chemo that are too toxic for their body, and some may receive too little to be effective.

A blood test can help determine the right dose; however going into the clinic for a blood test can be cumbersome and inconvenient for women with breast cancer. On a national scale drawing blood samples and transporting them around Australia to labs for analysis is logistically unfeasible for the health system.

Professor Jennifer Martin

Professor Jennifer Martin

NBCF is funding Professor Jennifer Martin’s project which aims to develop a new way of measuring the right dose for each person, which is similar to the finger prick blood test diabetics take several times a day to check their glucose levels.

This finger-prick blood sampling method could be done by health professionals who administer chemo at clinical facilities right across Australia, including remote and regional areas. The test would provide instant information on chemotherapy levels in the blood to assist in accurately tailoring the dose for each individual.

For patients already being treated, the test would also help determine if their dosage needs tweaking to get the best effect from the treatment while minimising side effects.

Achieving appropriate doses of chemotherapy in patients with breast cancer will contribute to improved management of breast cancer care, leading to better survival and better quality of life.

Improved early detection is a critical step in improved outcomes from breast cancer and BreastScreen Australia runs a breast screening program which is proven to reduce deaths from breast cancer.

The screening program schedules all eligible women for a mammogram every two years. However, not every woman has the same level of risk of breast cancer. Some women have a very low risk and some women have a higher risk so this fixed schedule may not detect any tumours early enough.

As our understanding of the risk factors for breast cancer increase – such as family genetics, breast density, obesity and other lifestyle factors such as alcohol – more powerful information could be incorporated into the screening process to provide a better understanding of a woman’s likelihood of developing breast cancer.

Dr Jocelyn Lippey

Dr Jocelyn Lippey

Cancer Australia is working on an improved breast screening program that includes these risk factors. This program will first require a trial of Australian women requiring breast screening to determine its suitability for nationwide adoption.

The success of the trial relies on women participating. The challenge is that with more information being collected and analysed by the new screening program, there may be significant changes to what women usually expect from their routine mammogram.

For example, as a result of her reviewing her risk of developing breast cancer, a woman’s routine screenings may be recommended to be more frequent if she is determined to be at high risk, or less frequent if she is low risk.

This type of divergence from current screening practice may be unsettling for women involved. How such a change in relation to their level of risk is communicated to women by healthcare providers is crucial to ensuring participation in the trial.

Women considering participating will need to fully understand any change to their schedule and feel confident that they are still receiving best-practice screening for breast cancer.

NBCF supports this initiative and has funded Dr Jocelyn Lippey to consult with women and healthcare providers on the most effective way to encourage women to participate in the trial.

Her study will ensure both women and their healthcare providers have the communication tools to understand what the tailored screening trial and subsequent nationwide program will involve, how it will run and what it can achieve, to give the trial and the subsequent program the best chance of being successfully implemented.

The spread of breast cancer, a process called metastasis, is the cause of death in nearly all patients who die of breast cancer.

Around a third of those diagnosed with breast cancer will later develop metastatic breast cancer, but as yet there is no way to know which patients will or when it might occur.

breast cancer researchMetastasis may happen up to 20 years after treatment for the original tumour, causing ongoing fear and anxiety for patients and their families about when or if the disease might come back.
Cancer cells can spread from the primary tumour and lodge in other tissues in the body, such as the bone marrow, and remain alive but not increase in number for many years – a process called metastatic dormancy.

Researchers have not yet discovered how a cell can stay alive but not divide and grow, and why it suddenly starts growing into a detectable secondary cancer.

The aim of this NBCF-funded project is to explore the role of a gene called c-Myc that can potentially control the dormancy of tumour cells and develop ways of  turning this gene on and off and test the ability of a cancer cell to stay dormant.

Professor Robin Anderson and her team are looking to see if dormant tumour cells use c-Myc to preserve their survival until conditions in the body are ideal to support rapid growth into a secondary tumour.

Until now, research into metastatic dormancy has been hampered by the lack of good ways in which to study the process, so Professor Anderson’s study has the potential for a breakthrough in understanding about how cancer returns and ultimately how to stop it.

Early detection increases the likelihood of breast cancer survival. While population-based breast screening provides the best chance of early detection, it doesn’t provide all women the same level of detection.

Unbeknownst to many women, the density of their breast tissue can impact on the ability of the mammogram to detect tumours. Dense breast tissue is coming to light as one of the strongest predictors of breast cancer risk – on par with carrying a mutation in the BRCA1 and BRCA2 genes.

On a mammogram, the white sections indicate dense breast tissue. Tumours also show up as white and can be obscured if a woman has dense breast tissue. If the mammogram is unable to distinguish a cancerous tissue from healthy dense tissue, tumours can go undetected.

It is becoming increasing clear that women need to be told about their breast density, both because of the impact of dense breast tissue on the effectiveness of a mammogram in finding cancer and because of the increased risk of breast cancer arising from high density.

Measuring breast density is on the cusp of becoming a useful health tool for women, however, more information is needed before it can be incorporated into public health programs.

Dr Jennifer Stone

Dr Jennifer Stone

In conjunction with BreastScreen WA, one of the only state-funded screening programs which informs women of their breast density, Dr Jennifer Stone aims to find out what women do with this information. She will survey women who receive the information about breast density and those that do not, to quantify perceptions, intentions and post-screening behaviour.

This study will be the largest and most comprehensive investigation thus far of the impact of informing screening participants that they have dense breasts and will provide the basis for BreastScreen programs to report measures of breast density to participants in future.

Dr Stone will also investigate the prevalence of dense breast tissue in specific populations, including Aboriginal women (for whom no information currently exists) and younger women (an established risk factor), to help inform public health improvements for these women.

The vast majority of women with breast cancer have oestrogen-receptor positive tumours. After their surgery, these patients will almost always be treated with endocrine however not all will require chemotherapy.

Belinda Yeo

Dr Belinda Yeo

This decision is usually based on an assessment of risk factors related to the tumour, its biology and the patient. There are multiple tests available that can help clinicians and patients to determine what the risk is of the cancer relapsing. One such test is called the Oncotype DX Recurrence Score. This test is very expensive (approximately $4000) and it not funded by Medicare and therefore remains inaccessible to most patients. This study evaluates a novel test called the IHC4+C score which estimates risk of the cancer coming back. For example, a risk score of 5% means that there is a 5% risk that the cancer could come back over the next ten years if the patient takes their endocrine therapy (and does not have chemotherapy). This score helps to decide whether chemotherapy should be recommended.

In the case of a score being 5%, this is considered a low risk score; hence it is unlikely that chemotherapy would be recommended to this patient. This test has been shown to provide similar information to the Oncotype DX but has the advantage of being affordable and routinely available. When used to help make treatment decisions, this test has been shown to result in less patients requiring chemotherapy.

Approximately 10 per cent of breast cancer cases are caused by faulty genes being handed down through generations. Those with familial breast cancer genes have a higher risk of developing the disease, are likely to get it at an earlier age and have a lower rate of survival than others with breast cancer.

BRCA1 and BRCA2 are well-known genes associated with a family history of breast cancer, but they don’t tell the full story – in about 50 per cent of families with a strong family history of breast cancer, the responsible gene is not known.

breast cancer researcher

NBCF-funded Dr Andrew Deans

The advent of genetic testing for genes associated with breast cancer has contributed to prevention and early diagnosis. There is room for improvement however as most of these tests are limited to looking for BRCA1 and BRCA2 genes, leaving many families with little information about their risk.

Attention is turning to two other genes, FANCC and FANCM, which evidence suggests could also be involved in familial breast cancer.

This study aims to determine the prevalence of FANCC and FANCM by analysing a large number of Australian familial breast cancer cases, and unaffected women, to see if adding these genes to standard genetic tests would be beneficial.

For women and men who have breast cancer in the family but test negative for BRCA1 and BRCA2, knowledge of other genes associated with a high risk of breast cancer is valuable information that can help them make informed choices about potential preventative measures that could mean they never develop breast cancer.

This national collaborative study led by Dr Andrew Deans will also aim to see if mutations in FANCC and FANCM follow a mechanism similar to that of mutated BRCA1 and BRCA2 genes in being unable to properly repair damaged DNA.

This could provide a better understanding of other genes that may also be associated to breast cancer, and point to opportunities for improving treatments for these families.

When breast cancer spreads to other parts of the body (a process called metastasis), cancer cells break away from the main tumour and move through the blood stream – the DNA from these tumour cells then appears in the blood and is called circulating tumour DNA, or ctDNA.

Researchers believe that analysing ctDNA could lead to the ability to predict, detect and monitor the return and spread of breast cancer.

breast cancer researcher

NBCF-funded Dr Louisa Lo

In this project, Louisa Lo will use advanced technology to read the genetic code of genes (gene sequencing) originally found within tumour cells and identify those that have undergone changes, mutated. She aims to find a biomarker for the most common type of breast cancer, estrogen receptor positive (ER+) breast cancer, of which around 30 percent will become metastatic at some point.

The advantage of analysing the ctDNA contained in a blood sample is that it contains information about all the genetic mutations that may occur at different metastatic sites in the body, information that can be missed by traditional tissue biopsies.

This will allow Louisa Lo means to map all of the gene mutations that occur in ER+ metastatic breast cancer, something which hasn’t been done before. This type of information may help classify patients so they can receive more personalised treatment in the future.

ctDNA may also be used to monitor how patients are responding to treatment, and this project will follow groups of patients receiving standard and targeted treatments to compare the results. This study could also provide insights into how resistance to treatment for metastatic breast cancer develops at the genetic level.

Research in this area is very promising if successful would be a major breakthrough in understanding what breast cancer is doing at any given time – information that will be welcome for patients who live in fear of their cancer returning and could provide doctors with another tool to help them save lives.

Australia’s national program of free mammographic screening for breast cancer is proven to save lives through early detection of the disease. New technology has the potential to be more accurate and to potentially save even more lives, but there are no data to inform whether this technology would be acceptable and effective for Australian women.

Digital breast tomosynthesis is a type of 3D-mammography which increases the accuracy of a breast scan by reducing layers of overlapping tissue that can mask tumours. It can also reduce the likelihood of false alarms, where the screening shows an area that looks like a tumour. A false alarm can be distressing for the women involved who may need further investigation to determine if they have breast cancer, and they place an additional burden on the health system.

Recent international trials have shown that adding 3D-mammography to 2D-mammography increases breast cancer detection, although worldwide the evidence is not yet conclusive about its health benefits.

Professor Nehmat Houssami

Professor Nehmat Houssami

For 3D-mammography to be recommended for adoption in Australia, evidence on its benefits based on use in local health programs is needed. In this study, NBCF-funded Professor Nehmat Houssami will conduct the first 3D-mammographic screening trial in Australia. Her data will provide critical evidence to assist policy-making decisions about the role of the new technology and whether a larger scale evaluation is needed.

Most evidence on tomosynthesis (3D) screening so far has used both 2D and 3D techniques, which is not ideal as it essentially doubles radiation exposure to the breast. In collaboration with BreastScreen Victoria, Professor Houssami’s pilot trial will examine a new, safer and potentially more effective way of screening using 3D-mammography which avoids the additional radiation exposure by extracting the 2D mammogram from the 3D images taken during screening.

The trial also aims to determine if Australian women are open to undergoing to a new type of screening, provide reliable estimates on breast cancer detection which will inform a larger trial, and prompt policy decisions about the adoption of 3D-mammography technology.

Breast cancer will affect one in eight Australian women and touch the lives of many families. About five per cent of breast cancer is due to an inherited gene defect – putting women and men in the family at risk. In order to understand, treat or even prevent these cancers, we need to study as many individuals from these families as possible.

kConFab is a resource for researchers and houses a collection of unique, detailed clinical, gene mutation data, blood and tissues on over 1700 breast and ovarian cancer families around Australia and New Zealand, information which is available throughout the world for ethically approved research.

Professor Stephen FoxIt is now clear that studying breast cancers that occur in these families can teach researchers a lot about some of the most deadly breast cancers that occur in young women without a family history of breast cancer, extending the influence of kConFab well beyond inherited breast cancer.

NBCF has supported kConFab for 20 years, allowing it to continue to maintain and expand as a world-class resource, enabling research into the lifestyle and molecular causes of breast cancer, strategies for prevention, new treatments and psychosocial factors that may impact positive health outcomes for these women and their families.

kConFab is the only publicly available resource which collects fresh surgical specimens of familial breast cancer; there is no similar resource in Australia or worldwide. Through kConFab, researchers in Australia and overseas can have access 20 years of accumulated biological samples linked to extensive data.

kConFab has galvanised breast cancer research by supporting 161 research projects, (many funded by additional grants from NBCF), including overseas collaborative projects, some with commercial intent.

 

The metastatic stage of breast cancer, when the cancer spreads beyond the breast, is treatable but not curable, and is the main cause of death from the disease.

A major hurdle to developing effective treatments for metastatic breast cancer is a lack of understanding, at a molecular level, of how and when cancer cells spread and grow.

Dr Paul Timpson

Dr Paul Timpson

Dr Paul Timpson has been funded by NBCF to work out a way to identify the earliest movement of breast cancer beyond the breast, and how it can be blocked at that point before it spreads to vital organs.

Dr Timpson and his team have previous success at blocking metastatic pancreatic cancer in mice. They used special nano-technology which glows to show when and where cancer cells are about to become metastatic.

They aim to recreate this success with metastatic breast cancer by combining the nano-technology with a surgically inserted titanium-framed glass window – its first application in Australia.

The researchers will be able to view live tumour cells inside the mice and watch what is happening at the earliest stages of metastasis which could help to predict the exact point that breast cancer begins to spread.

The ability to predict and stop cancer’s spread to vital organs would be a crucial breakthrough in breast cancer. The discovery could lead to effective treatments that prevent primary tumours invading other parts of the body, and determine the best timing for administering treatments.