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NEW HOPE FOR STAGE 4 BREAST CANCER PATIENTS

The SEGMENT study examined the feasibility of characterising genomic alterations using gene sequencing on tumour specimens from patients with breast cancer.

The SEGMENT Study

Metastatic (stage 4) breast cancer is incurable, but a new study suggests that genomic profiling could lead to better treatment options for patients.

The SEGMENT study examined the feasibility of characterising genomic alterations using gene sequencing on tumour specimens from patients with breast cancer.

The study found that genomic sequencing for the management of metastatic breast cancer is both feasible and has implications for clinical practice, particularly for patients who are able to participate in clinical trials of newer treatments.

The project, which was spearheaded by Professor Sherene Loi at the Peter MacCallum Cancer Centre, received funding from Breast Cancer Trials.

“Patients with metastatic breast cancer are looking for anything that can give them hope,” says medical oncologist Dr Peter Savas, Dr Loi’s colleague at the Peter MacCallum Cancer Centre. “SEGMENT was about trying to use what was at the time quite a new technology, and bring it into the clinic to see if we could use that to give patients more options.”

The development of Herceptin – a drug that targets overactivity of the HER-2 gene in one of the more aggressive types of breast cancer – in the 1990s, opened the door to better-targeted therapies.

“Now, the prognosis of that cancer is significantly better,” Dr Savas says. “That’s a really good example of the proof of principle that tailoring treatments to specific features in the cancer can be very fruitful. The next logical question is, can we take that approach and make it more broadly applicable to patients with metastatic breast cancer?”

Meanwhile, sequencing technologies – relatively rare when SEGMENT began in 2013 – have become cheaper and more accurate, making profiling of metastatic breast cancer more available.

One barrier to that, Dr Savas says, is a lack of awareness among oncologists and patients. “But that’s improving over time, and the pairing of genomic findings with treatments will become more widespread.”

Launched in 2019, the drug alpelisib is one example of this. It specifically targets the PIK3CA mutation, which is common in many patients with hormone receptor positive breast cancer, Dr Savas says. “Following that, there’s a long tail of rarer alterations,” he adds.

“SEGMENT is a big study, but it doesn’t have enough patients to understand the importance of rarer alterations. But by putting it together with other datasets, we can get a better idea of the changes and their significance.”

 

Publication:

Clinical implications of prospective genomic profiling of metastatic breast cancer patients.
van Geelen CT, Savas P, Teo ZL, Luen SJ, Weng C-F, Ko Y-A, Kuykhoven KS, Caramia F, Salgado R, Francis PA, Dawson S-J, Fox SB, Fellowes A, Loi S. Breast Cancer Research. 2020; 22:91:https://doi.org/10.1186/s13058-020-01328-0.

 

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Professor Sherene Loi

Professor Sherene Loi is a Breast Cancer Trials researcher and board director, consultant medical oncologist, clinician scientist, head of the Translational Breast Cancer Genomics and Therapeutics laboratory at the Peter McCallum Cancer Centre and Co-Chair of the IBCSG.

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PREVENTING THE SIDE EFFECTS OF PREVENTATIVE TREATMENT

A follow up on the IBIS-II clinical trial has evaluated the side effects of the breast cancer preventative agent Anastrozole and how they can be managed.

Preventing The Side Effects Of Preventative Treatment

The saying ‘prevention is better than a cure’ is especially apparent when it comes to disease. But, while breast cancer prevention remains crucial, the side effects of individual treatment plans also need to be considered.

Anastrozole is a drug that is used to either prevent or control breast cancer. It’s a tablet that works by blocking the body’s production of oestrogen in postmenopausal women. It’s taken to prevent cancer recurrence, or control cancer that has spread to other parts of the body. It also reduces the chance of breast cancer in women with a higher risk of developing the disease by 50 per cent.

“So, why don’t we just give this drug to all women? Because of its potential side effects,” says Dr Nicholas Zdenkowski, Medical Advisor at Breast Cancer Trials.

He says a relatively common effect is one that would likely go unnoticed initially: bone density loss.

“This won’t be obvious until you end up with a bone fracture or see a decline in bone density on a scan,” he says.

Dr Zdenkowski was the Australian clinical lead on an international study to see if the drug risedronate could prevent anastrozole-induced bone loss.

The trial was co-led by Breast Cancer Trials and was a sub-study of the 4,000 post-menopausal high-risk patients already on the IBIS-II clinical trial that showed that anastrozole could prevent breast cancer.

This bone sub-study involved 258 of the 1,410 patients (229 from Australia and New Zealand) who enrolled in the bone study within IBIS-II. It found risedronate did indeed slow down anastrozole-induced bone loss – but couldn’t completely prevent it. While the drug stabilised loss in the lumbar spine, the hip still deteriorated.

“The options for breast cancer prevention include anastrozole, exemestane and tamoxifen, but they all come with their own set of potential side effects,” Dr Zdenkowski says.

“While bone density is something that naturally declines slowly over time, unfortunately anastrozole adds to that decline.”

He says more options are needed for patients on breast cancer prevention drugs.

Dr Zdenkowski suggests patients have their bone density monitored regularly so that osteoporotic changes are identified and treated accordingly, before the stage where they are at significantly higher risk of hip or spine fractures.

He said overall, the lessons learned from the risedronate trials tie into important decisions around preventative treatment plans. This includes, for patients with a high risk of breast cancer combined with a high risk of bone loss, whether to put them onto alternative treatments to counter the development of osteoporosis.

“There is obviously more work to be done on the prevention of breast cancer,” Dr Zdenkowski says. “The more we know, the more this helps with clinical decisions around the risk vs benefit of treatment recommendations.”

Publication:

Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia. Sestak I, Blake GM, Patel R, Colemen RE, Cuzick J, Eastell R. Bone. 2019; 124:83-88, https://doi.org/10.1016/j.bone.2019.04.016.

 

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Dr Nicholas Zdenkowski

Dr Nicholas Zdenkowski is the Medical Advisor at Breast Cancer Trials, a BCT researcher and medical oncologist.

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BENEFITS OF EXERCISE FOR BREAST CANCER PATIENTS

We speak with Professor Erica James about the benefit of exercise for breast cancer patients, how lifestyle changes can help to reduce the risk of recurrence and the best ways to get active after a diagnosis.

IS it OK To Exercise With Breast Cancer?

More than 40% of new cancer cases are linked to lifestyle factors, and about one third of all cancers are preventable through a healthy diet, being physically active and maintaining a healthy weight.

The link between good health and exercise is well established and more cancer practitioners are prescribing exercise as part of treatment plans for their patients.

But with treatment comes many different side effects and physical changes that can make the idea of getting out for a run or hitting up a body pump class incredibly undesirable.

However, even small lifestyle changes during and after treatment can reduce the side effects of treatment, improve quality of life, and reduce the risk of breast cancer returning.

Exercise scientist and behavioural epidemiologist at the University of Newcastle and the Hunter Medical Research Institute (HMRI), Professor Erica James, said the side effects of treatment can be, at times, debilitating for patients, but it’s important at this time to engage in healthy behaviours that will aid in recovery.

“I have had patients tell me they have been tired before, they have had small children, done shift work, had interrupted sleep. They thought they knew what it felt like to be tired. But this (cancer related fatigue), it’s a whole new world.”

Professor James acknowledges that it can feel counter-intuitive to move rather than rest at this time, but, creating good sleep habits and incorporating movement into the day, will help to improve quality of life and increase your energy throughout the day.

She said that being active and having good sleep hygiene is important. This means avoiding naps during the day, avoiding caffeine after lunchtime, and having a regular bedtime routine.

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We speak with exercise scientist and behavioural epidemiologist Professor Erica James, about the benefit of exercise during and after a diagnosis, how lifestyle changes can help to reduce the risk of breast cancer recurrence, and the best ways to get active after a diagnosis.

So how much should you be exercising?

Professor James said that the exercise and movement recommendations for those who have received a breast cancer diagnosis are similar to that of the general population. 150 minutes of moderate to vigorous activity a week, or at least 30 minutes of movement on at least five days of the week, is recommended, as well as two or three strength-based activities.

However, each individual will be different.

“Whenever there’s been a major medical issue like a cancer diagnosis, it’s really important that the exercise prescription can be tailored to the person’s individual circumstances,” said Professor James.

This is where expert advice can be really helpful.

In Australia, the organisation that looks after exercise prescription is called ESSA (Exercise and Sports Science Australia). This professional organisation accredits exercise physiologists and ensure they can safely prescribe a personalised exercise plan for those who have chronic diseases like cancer.

You can use the ESSA website to find an accredited exercise professional that can help you get moving safely.

You can enter your postcode and special interest area (for example, cancer) and find someone suitable close to you.

Professor James also acknowledges that this can be an expensive endeavour in an incredibly tough financial time of a person’s life. She said that, in this case, a patient should approach their GP about getting Medicare subsidised assistance.

“In Australia, we have a fantastic system that’s Medicare funded, called a chronic disease management plan.”

“You can go to your GP and say I want to see an exercise physiologist.”

“They write you a chronic disease management plan and you get up to five Medicare subsidized visits with an exercise physiologist in a 12-month period.”

Professor James said in these subsidised visits, you can get an assessment, get taught how to do the exercises safely and have a tailored, personalized plan written just for you.

How can I start moving?

Professor James said that it’s important that you enjoy the exercise you undertake.

“So if you start a walking program, are there great podcasts that you love to listen to?”

“We also know that people who own dogs are more active. They’re more motivated to still get out and walk even if the weather is bad or they are feeling tired.”

“Reflect on where you have had success before. What can I integrate into my lifestyle that’s likely to be able to be maintained?”

She also said that starting small is the best first step and that any movement is better than no movement at all.

“It’s certainly not about jumping straight into a seven day a week high intensity exercise program.”

She recommends starting by reframing what exercise is in your mind and weaving exercise into your everyday life. For example, instead of trying to get the closest car park you can, park a little away from your destination and make the most of the walk. Setting goals, making a plan, and getting your friends and family on board are important strategies to ensure you can maintain activity in the long term.

What questions should I ask before exercising?

Before you begin your exercise treatment plan, you should discuss your physical capabilities with your treatment team.

“Some key questions that you might want talk to your doctor about is clarifying whether you have an increased risk of bone fracture.”

“If you’ve got low bone mineral density, if you’re postmenopausal, if you’re older, or if the cancer has spread to your bones, then you might be at an increased risk of breaking a bone if you were to have a fall.”

“In those cases, we would recommend lower impact exercises like walking, swimming or yoga, and modifications if balance is an issue, such as chair-based exercises.”

“If you’re having active treatment, another question to ask your treatment team would be, am I at increased risk of infection?”

“If, for example, you’re undergoing chemotherapy and you’ve got a reduced white cell count, but you want to go swimming in the local pool, it would be helpful to clarify your current risk and make a plan around that.”

Professor James strongly recommends those with a cancer diagnosis visit an accredited exercise physiologist to ensure they are moving appropriately for their situation.

However, if a patient would prefer to see a personal trainer, or engage in group fitness, she encourages them to ask if they have experience training someone with a cancer diagnosis. If they are willing to provide modifications to exercises that are appropriate to your individual situation and if they have any qualifications to train someone in your situation.

Can these changes help reduce my risk of cancer returning?

Professor James said these lifestyle changes can be incredibly helpful in maintaining a good quality of life throughout and post treatment, as well as helping to maintain good mental health and reduce the effects of treatment side effects.

She also said that exercise has a significant impact on helping to reduce the risk of breast cancer returning and the risk of death from breast cancer.

A review of the effect of lifestyle factors on breast cancer mortality found that physical activity is consistently linked to a lower risk of breast cancer recurrence.

A large study showed that women who exercised moderately (the equivalent of walking three to five hours a week at an average pace) following a breast cancer diagnosis had 40% to 50% lower risks of breast cancer recurrence and death from breast cancer or any cause, compared with women who exercised less.

The benefit of exercise was particularly apparent in women with hormone-responsive breast tumors.

So although it may seem like the very last thing you want to do while undergoing treatment, the evidence is clear; healthy eating, good sleep and exercise is important to maintain after receiving a diagnosis.

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Professor Erica James

Professor Erica James is a exercise scientist and behavioural epidemiologist at the University of Newcastle and the Hunter Medical Research Institute (HMRI).

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ESMO 2020: BREAST CANCER RESEARCH SUMMARY

A summary of some of the key presentations and breast cancer announcements at ESMO Immuno-Oncology Virtual Congress 2020.

European Society For Medical Oncology 2020

Every year, the European Society for Medical Oncology (ESMO) hosts its annual conference, bringing together almost 30,000 clinicians, researchers and patients advocates from around 140 countries.

These oncology professionals share their latest research and advances in treatments and help to translate the latest science into better patient care.

However, like most events this year, ESMO 2020 had to pivot to an online format, allowing researchers to participate across multiple different time zones to ensure they could hear the latest research results and work towards finding new and better treatments for their patients.

New and exciting breast cancer research was presented, and we have provided a summary of some of the key presentations below:

MonarchE Trial Results: Breakthrough In High Risk HR+ Breast Cancer Patient Treatment

The MonarchE clinical trial results have been described as promising for patients with early stage HR+ breast cancer.

Around 70% of breast cancer patients are diagnosed with hormone receptor positive (HR+) disease. Those with HR+ disease that has spread to the lymph nodes, have a large tumour size when diagnosed or have increased cellular proliferation, are considered to be of high risk of recurrence.

These patients were recruited to the MonarchE trial as they had a higher risk of their breast cancer returning in the first two years.

The MonarchE trial found a 25 per cent reduction in recurrence of cancer within the first two years when the CDK 4/6 inhibitor abemaciclib was added to the standard hormone therapy, compared with the hormone therapy alone.

The phase three clinical trial was conducted worldwide and was led by UK researchers. It involved 5,637 patients in 38 countries. Researchers will continue their follow-up assessments to see if the benefit of this treatment continues beyond the two years measured.

SOLAR-1 Trial Results: Survival Benefit For Advanced Breast Cancer Patients With limited Treatment options

Some patients with HR positive, HER2 negative advanced breast cancer could see improved survival thanks to a new drug combination. The SOLAR-1 clinical was open to patients with HR-positive, HER2-negative advanced breast cancer.

This analysis focussed on those who had the PI3KCA gene mutation, which was previously shown to benefit most from a PI3K inhibitor, alpelisib. It showed that by giving this group of patients alpelisib with fulvestrant, patients had an overall survival benefit of eight months, compared to a group taking a placebo and fulvestrant.

It is thought that the PI3K pathway (important in cell growth and survival) can become very active in cancer cells because of mutations in the PIK3CA gene, and that this pathway may be important when resistance to CDK4/6 inhibitors and endocrine therapy develops.

About 40% of HR-positive, HER2 negative breast cancers have a PIK3CA mutation. PIK3CA mutations can be found by testing tumour tissue or blood. A blood test is easy to perform, safe, less invasive than a tumour biopsy and can be repeated regularly.

These results are encouraging as they further support the use of alpelisib plus fulvestrant for patients with HR-positive, HER2-negative advanced breast cancer and PI3KCA mutations, a setting in which treatment options are very limited.

It also gives confidence to the Breast Cancer Trials CAPTURE study that is currently open to patients in Australia.

The CAPTURE clinical trial will check approximately 400 patients with ER+, HER2 negative breast cancer via a blood test to see if they have the PIK3CA gene mutation in ctDNA.

Those participants who have a confirmed PIK3CA gene mutation (approximately 140 (35%)) will be randomised 1:1 to receive alpelisib and fulvestrant (Arm A) or the standard treatment capecitabine (Arm B).

IMpassion 031: Encouraging News For Early Triple Negative Breast Cancer Patients

Data presented at ESMO 2020 from the IMpassion 130 clinical trial is encouraging for patients with early stage triple negative breast cancer.

The IMpassion 031 clinical trial found that neoadjuvant (pre-surgery) treatment with the immunotherapy drug, PD-L1 inhibitor atezolizumab, was associated with a significantly greater pathological complete response rate (no cancer cells left after treatment) when combined with standard chemotherapy.

The patients receiving the trial treatment had a pathological complete response rate of 57.6%, compared with 41.1% for those on chemotherapy alone, in previously untreated patients with early triple negative breast cancer.

IMpassion 031 is a phase three clinical trial that enrolled those with stage two or three triple negative breast cancer. Patients received neoadjuvant atezolizumab or placebo plus nab-paclitaxel followed by standard dose-dense chemotherapy with doxorubicin/cyclophosphamide, prior to surgery. Atezolizumab or placebo was continued after surgery to complete one year of therapy.

Research into triple negative breast cancer is important, as this tumour type is typically associated with earlier recurrence and metastatic spread compared to other forms of breast cancer.

IMpassion 131: Results For Metastatic Triple Negative Patients Not As Encouraging As IMpassion 130 Results

Adding atezolizumab to paclitaxel does not improve progression-free survival or overall survival in patients with locally advanced or metastatic triple negative breast cancer, according to results from the Impassion 131 clinical trial presented at ESMO 2020.

The results of Impassion 131 showed that there was no significant difference between the atezolizumab and placebo arms in their response rates. The findings are in contrast to the IMpassion 031 study above, which enrolled patients with early stage breast cancer rather than metastatic, used nab-paclitaxel instead of paclitaxel. The researchers who led this study have said the potential reasons for such a difference between the two trials requires “further exploration.”

HER2CLIMB: Drug Shown To Improve Survival And Quality Of Life For Patients With HER2-Positive Metastatic Breast Cancer

Results from the HER2CLIMB clinical trial presented a ESMO 2020 has shown that the addition of the drug tucatinib (Tukysa) to trastuzumab (Herceptin) and capecitabine (Xeloda) significant improved progression-free survival and overall survival in patients with HER2-positive metastatic breast cancer, with and without brain metastases.

The results showed that, taken together, this treatment regimen improves survival for this group of patients but also maintains quality of life. In this total cohort of patients on the trial, the risk of death was reduced by 34%. The primary end point of progression free survival by blinded independent central review was assessed in the first 480 patients enrolled.

Overall, risk of progression or death was reduced by 46%. In patients with brain metastases, risk of progression or death was reduced by 52%.

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WHAT HAPPENS DURING A CLINICAL TRIAL?

Clinical trials are an important part of our health system and we answer some frequently asked questions about what happens during a clinical trial.

What Is A Clinical Trial?

Clinical trials are an important part of our health system and are necessary to find out if new treatments are more effective than those currently accepted as the best available standard of care. They are designed to answer a scientific question and compare whether a new treatment is better than the current treatment. In fact, the current treatments that are saving lives today are typically only available because clinical trials have shown that they are beneficial.

All new breast cancer treatments or prevention strategies must be rigorously tested through the clinical trials process before they are made widely available to the community. This includes chemotherapy and hormone treatments to prevent recurrence and save lives, mammograms and breast cancer surgeries.

Who Participates In A Clinical Trial?

People who participate in a clinical trial volunteer to do so. In terms of breast cancer clinical trials, participants have been diagnosed with breast cancer or in regard to prevention trials, are at higher than average risk of being diagnosed with breast cancer.

Participants in any clinical trials need to understand what is going to be involved. This is the process of informed consent, before signing onto a trial. The treating physician and clinical trial coordinator will go through this information with the potential participant. This will include an explanation of the trial protocol and provision of written participant information and consent forms. They will discuss the trials aims, potential side effects and what kind of trial it is. Potential participants are given time to read about it, ask questions, discuss with their friends, family and other health professionals before deciding to enter the trial.

Is It Safe To Participate In A Clinical Trial?

Yes.

The health and safety of clinical trial participants is the first priority in the trials process. By the time a treatment is used in a clinical trial, it has already gone through exhaustive testing. It will then be used very carefully in a trial with a small number of volunteers to ensure safety, before larger trials are done to find out if it effective against cancer. These trials are designed by doctors and researchers who are highly respected leaders in their field, with the support of rigorous scientific evidence.

As with any medical treatment, there is the possibility of side effects. However, the treatments are developed and tested so that the doses used are not expected to lead to excessive side effects, and that those possible side effects have treatment strategies available. The potential side effects are explained to the person before they choose to enter into the trial, to ensure that they are making an informed decision.

The research is overseen by independent people who are not involved in the initial trial development process. This is done by checking through the clinical trial protocol, which outlines the reason for doing the study, who may participate, the treatments and tests involved, when these will be done and why. This independent panel of scientists, medical professionals and consumers is called an ethics committee. The progress of the clinical trial and the safety of clinical trial participants is carefully reviewed and monitored by an Independent Data and Safety Monitoring Committee and by the ethics committee responsible for approving the clinical trial.

Before joining a clinical trial, potential participants must understand why the clinical trial is being conducted, the potential risks and benefits and what their involvement would include. The decision to participate is made on the basis of information provided to the patient by their treating doctor.

A trial participant can choose to remove themselves from the clinical trial at any time. A patient’s treating doctor can also choose to take the participant off the trial if they believe they are having an adverse reaction to a treatment. If a treatment or intervention being tested in a clinical trial is showing no benefit to participants, then the researchers conducting the study will decide if all participants should be taken off the treatment or intervention being trialled.

What Phases Are Involved During A Clinical Trial?

Clinical trials are generally conducted in four phases. Each phase is designed to answer certain scientific questions.

Phase One Clinical Trial

Phase 1 clinical trials are conducted to test a new biomedical intervention (treatment) for the first time in a small group of people (around 20 to 50 people) to evaluate the safety and side effects of the new treatment or intervention. Phase 1 trials are not usually randomised.

Phase Two Clinical Trial

If the treatment or intervention is proven successful in phase one, it is moved to a phase 2 study and tested in a larger group of people (generally several hundred) to give an indication of how effective it is and to further evaluate its safety.

Phase Three Clinical Trial

Phase 3 clinical trials compare new treatments with the best currently available treatment (standard treatment). Phase 3 clinical trials study the efficacy of a treatment or intervention in large groups of people (several hundred to several thousand). They look at which treatments work best for the disease, how the treatment affects quality of life and learns more about side effects. A phase 3 clinical trial could compare the standard treatment with a new treatment, a different dose of the same treatment or a different way of giving the same treatment. These are usually randomised, meaning that participants are allocated to one of two or more treatment options at random, and neither they or their doctors get to choose which treatment. Determined This helps to remove any biases that could lead to false conclusions being made about the effectiveness of the new treatment. Importantly, with this type of trial, participants are given the current standard of care at a minimum, and the new treatment is hoped to be better than that standard care (or at the minimum, no worse).

Phase Four Clinical Trial

A phase 4 clinical trial is conducted after the new treatment or intervention has been approved and entered routine clinical practice. A phase 4 clinical trial aims to learn more about the side effects and safety of the new treatment, the long-term risks and benefits of the new treatment and how effective the treatment is when used in the general population over a longer period of time.

How Long Do Clinical Trials Take?

The length of a clinical trial is dependent on what kind of trial and treatment is being tested. This means each clinical trial timeline is different and we cannot say definitively how long each phase of a clinical trial will last. If you are considering signing on to a clinical trial, this information will be communicated to you by your treating doctor and the clinical trial coordinator. The following information is intended only as a guide and may not be relevant to your individual situation:

Phase 1 trials may last less than a year as these trials are testing in small groups and evaluate the safety of a new treatment or drug. However, if the patient is benefiting from the treatment, the patient may continue on the clinical trial and treatment for longer. This is dependent on individual circumstances.

Phase 2 trials may be longer than phase 1 trials as there are more participants, which means recruitment may take longer. Though recruitment may take longer, patients may be on the treatment for a similar time to those on a phase one trial.

Phase 3 trials, the most common phase trials, may take longer than phase 1 and 2 clinical trials, but the duration depends on the size of the clinical trial, what stage of cancer is being treated and what the determined end points for the clinical trials. For example, the large adjuvant clinical trials SOFT and TEXT have been going on for around a decade, with follow-up still occurring. This does not mean patients are still receiving active treatment, but it does mean researchers are still examining the benefit of the treatment patients received through follow-up consultations.

Phase 4 trials can last for a few years to more than a decade as it is testing the long-term risks and benefits of a new treatment in a larger population, over a longer period of time.

What Happens When A Clinical Trial Ends?

When a clinical trial has reached its determined end point, the researchers involved in the study will evaluate all the information collected. An analysis is also usually conducted during the clinical trial. All this information collected during and post- trial will help to determine if the treatment or intervention should continue to the next phase of the clinical trial, or if the treatment or intervention should be approved for use in the clinic by the relevant health authorities. Once a new treatment has been proven in a clinical trial, the addition of this treatment to the Pharmaceutical Benefits Scheme (PBS) in Australia and PHARMAC in New Zealand, is a separate process and can take several years.

There are a lot of factors that determine how long it will take for a safe and effective treatment to be approved for use in the clinic. Larger trials that have had thousands of participants will take longer to evaluate than smaller trials. This can take a number of years.

Participants are also usually involved in follow-up for years after their involvement in the active treatment part of a clinical trial. This means they are monitored for many years after their active involvement has finished, including when they have finished taking the treatment tested in the clinical trial. This follow-up could include filling in a survey each year or receiving check-ups with your treating doctor. This helps researchers study the long-term effects and efficiency of the treatment or intervention studied.

If you have participated in a clinical trial, the researchers should make the results of the study available to you directly when they become available. Results are generally presented in reports or published in scientific journals.

Can I Participate In Two Clinical Trials At Once?

Generally, researchers prefer clinical trial participants to be involved in only one clinical trial at a time. This is so they can clearly attribute the risks and benefits of each treatment or intervention to the clinical trial. There are exceptions; however, clinical trial participants can be involved in a therapeutic trial and a tumour banking trial, a quality of life or lifestyle intervention trial simultaneously. Your treating doctor will advise on what trials you can participate in.

Can I Discuss The Clinical Trial With My Family And Friends?

Yes!

Your doctor and clinical trial team will encourage you to discuss your participation in clinical trials with trusted loved ones so you can feel confident in your choice to participate. Additionally, the more people who are aware of and understand clinical trials the better. This helps to increase participation in clinical trials which helps to further breast cancer research and help to find new and better treatments and prevention strategies for the disease. You may also wish to discuss the trial with other health professionals such as your GP prior to participation.

Will My Details Be Published To The Public?

No.

Patient privacy is of the utmost importance is the clinical trials process. Once you consent to take part in a clinical trial, your information will form part of the clinical trials records and be processed in line with the applicable laws that control clinical trials. This means that identifying information such as name, date of birth and address are removed from your information, and replaced with a code, so that the researchers analysing the information cannot identify you as an individual. In any case, the trial information is generally only meaningful when it is analysed as a group, not from any one participant on their own.

When participating in a Breast Cancer Trials clinical trial, your confidential health information will only be accessed by people involved in the clinical trial, including health care professionals and Breast Cancer Trials research staff who are all dedicated to upholding the rights of trial participants to privacy. Any identifying details are removed by your treating doctor or clinical trial coordinator prior to the data being send to the data repository, for example the Breast Cancer Trials database.

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AUSTRALIAN BREAST CANCER RESEARCHER IN RACE TO FIND CORONAVIRUS VACCINE

Dr Ross Jennens is one of 4,000 Australian health professionals participating in the BRACE clinical trial.

The BRACE Clinical Trial

Dr Ross Jennens is a member of Breast Cancer Trials and is a Medical Oncologist at the Epworth Hospital in Melbourne.

He has been involved in the conduct of a number of clinical trials including the TEXT clinical trial, which produced practice changing results in the treatment of young women with breast cancer.

But with rise of COVID-19 in our community, Dr Jennens is now one of 4,000 health professionals in Australia who are participating in the BRACE clinical trial.

This study aims to test the BCG vaccine, which was developed to prevent tuberculosis and is commonly used as a treatment for people with bladder cancer, to see if it can provide an immune system boost to protect people from COVID-19 symptoms.

We asked Dr Jennens how this Australian trial was developed and what’s involved for health workers.

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Dr Ross Jennens discusses his participation in the BRACE Clinical Trial.

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Dr Ross Jennens is Breast Cancer Trials Researcher and a Medical Oncologist at Epworth Hospital in Melbourne.

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BREAST CANCER RECURRENCE RATES: UNDERSTANDING THE RISK THAT YOUR CANCER WILL RETURN

The rate of breast cancer recurrence is not the same for all patients. Understand the risk of recurrence for your type of breast cancer.

Understanding the Likelihood of Breast Cancer Recurrence Rates

Fear of recurrence – that is, the fear your breast cancer will come back – is a common issue facing women who’ve had early stage breast cancer. Fortunately, Australia has one of the best survival rates of breast cancer in the world, with 91% of women surviving at least five years past their diagnosis. New Zealand is not far behind with 88% of women surviving five years past their first diagnosis.

This information may come as a relief for those diagnosed with early stages (stage 1-3) of the disease, as many recurrences appear within five years after the initial treatment, the exception being ER positive breast cancer, as many recurrences will occur after the first five years as within the first five years. The rate of recurrence is not the same for all breast cancer types or patients. Understanding the risk of recurrence for your type of breast cancer may help to ease some anxiety.

What Is Breast Cancer Recurrence?

Breast cancer recurrence means that the cancer was diagnosed when limited to the breast and/or armpit lymph nodes, then treated, and at some time later has come back.

Breast cancer recurrence occurs in three main ways:

  • Local recurrence: the breast cancer that was previously treated returns within the breast or armpit lymph nodes.
  • New primary breast cancer: an unrelated new breast cancer occurs in one or the other breast.
  • Distant recurrence: The previously treated breast cancer returns in other parts of the body, such as the bones, liver or lungs.

Breast cancer recurrence occurs if:

  • Cells from the original breast cancer diagnosis break away and hide nearby in the breast (called local recurrence) or spread elsewhere in the body (called distant recurrence); AND
  • Treatment, including surgery, chemotherapy, radiotherapy and/or hormone therapy have not gotten rid of all these cancer cells from the body.

These cells can begin to grow right away or can remain dormant for many years before beginning to grow and travel further through the body.

Many breast cancer recurrences are detected in the five years after diagnosis, especially after triple negative breast cancer. However, recurrence can occur more than 20 years after the first diagnosis.

Breast cancer survivors are at risk for developing new cancers for a number of reasons – whatever caused the original cancer could still be having an effect, either on second primaries in the same organ, or on related cancers in other organs. This can be due to genetic predisposition, as is sometimes the case with breast cancer.

What are the Breast Cancer Recurrence Rates for Australia and New Zealand?

Unfortunately, Australia and New Zealand don’t keep track of breast cancer recurrence rates, so it is hard to state the chance of breast cancer returning for the whole population of those diagnosed with breast cancer.

Your individual chance of breast cancer returning depends on a number of factors including the type of breast cancer, tumour size, genetic factors and treatment types.

See more on risk factors for breast cancer recurrence.

What Types of Breast Cancer have the Highest Recurrence Rates?

A study published in the Journal of Clinical Oncology found the rate of recurrence for all breast cancers was highest in the first five years from the initial cancer diagnosis at 10.4%. Specifically, the risk was highest between the first and second years after the initial diagnosis.

During the first five years after the initial diagnosis, patients with oestrogen receptor (ER) positive breast cancer had lower rates of recurrence compared with those with ER negative disease. However, beyond five years, patients with ER positive disease had higher rates of recurrence.

Who Is At Risk Of Breast Cancer Recurrence?

Everyone who has received a breast cancer diagnosis is at risk of recurrence, however the risk differs markedly depending on a number of factors listed below.

  • Lower risk recurrence: Some breast cancer, when diagnosed very early when small and without lymph node involvement, have an excellent prognosis and are very unlikely to recur.
  • Greater risk of recurrence: Larger cancers, with lymph node involvement or with a more invasive behavior, unfortunately have a higher risk of returning.

What Factors Contribute To The Risk of Breast Cancer Recurrence?

Whilst it is never completely certain that breast cancer has been cured, there are many treatments available that reduce the risk of recurrence. There are also a number of risk factors that can contribute to the rate of breast cancer recurrence.

  • Your age at first diagnosis: Younger women, particularly those who had their first diagnosis under the age of 35, have a greater risk of breast cancer. This is because those diagnosed at a young age are more likely to have aggressive features in their breast cancer. Additionally women diagnosed with breast cancer before menopause have a greater risk of recurrence.
  • Tumour size: Women who have a larger breast tumour have a greater risk of recurrence.
  • Lifestyle factors: Excess weight is associated with a higher risk of postmenopausal breast cancer and is also associated with a higher risk of breast cancer recurrence and death. Smoking has also been shown to increase the risk of recurrence. Women who exercise regularly (at least half an hour per day of moderate intensity exercise, 5 days per week) appear to have a lower rate of breast cancer recurrence.
  • Lymph node involvement: If cancer is found in lymph nodes at the time of the original breast cancer diagnosis, there is an increased risk of breast cancer recurrence. This is the strongest prognostic factor, and the more nodes involved, the higher the risk of recurrence.

How Does The BRCA1 or BRCA2 Gene Mutation Affect My Risk Of Breast Cancer Recurrence?

Women with a BRCA1 or BRCA2 gene mutation and who have already been diagnosed with breast cancer, have a higher-than-average chance of new primary breast cancers than those without this genetic mutation. The rate of local or distant recurrence depends on the type and stage of the original breast cancer, and is no different from a non-BRCA-mutated breast cancer.

For women with a BRCA1 or BRCA2 gene mutation, the rate of contralateral breast cancer, or cancer in the opposite breast to the original cancer, 10 years after diagnosis of the first cancer is about 10-30 percent, compared to about 5-10 percent for women diagnosed with breast cancer who do not have a BRCA1 or BRCA2 gene mutation.

Women who have a BRCA1 or BRCA2 gene mutation and have received a breast cancer diagnosis should talk to their treatment team about their options to reduce their risk of breast cancer recurrence.

What Are The Signs Of Breast Cancer Recurrence?

If you have a local recurrence or new primary breast cancer, you may find symptoms similar to an initial breast cancer.

These include:

  • A new lump in the breast, armpit area or around the collarbone
  • A change in breast size or shape
  • Changes to the nipple, such as sores or crusting, an ulcer or inverted nipple
  • Clear or bloody nipple discharge
  • Changes to the skin including redness, puckering or dimpling (an ‘orange peel’ appearance)
  • Breast tenderness or pain

If your breast cancer has spread to other parts to the body, known as distant recurrence, there are a number of possible symptoms, including:

  • Fatigue
  • Breathlessness
  • Pain in your bones
  • Unexpected weight loss or change in appetite
  • Severe or ongoing headaches
  • Nausea

However, symptoms will vary depending on where the secondary cancer presents, and some primary and secondary cancers may not present any obvious symptoms. Sometimes breast cancer recurrence is identified on a scan or blood test that was done for a reason other than the cancer itself.

If you have any health concerns or symptoms that are new or persistent, speak with your GP or treating physician.

Should I Have Scans Or Blood Tests To Check For Breast Cancer?

After a diagnosis of early stage breast cancer, any remaining breast tissue should be evaluated with scans (such as mammogram or ultrasound) regularly. The frequency is often annually but is best discussed with your specialist(s).

Current guidelines and evidence recommend against routine CT or bone scans, or blood tests, to look for recurrence of cancer in patients who do not have any symptoms or other concerns that need to be followed up on. These tests have not been shown to improve outcomes and cause unnecessary ‘scanxiety’. If you do have concerning symptoms (such as those mentioned above), then you should bring them to the attention of your healthcare team to be checked out.

Am I Still At Risk Of Breast Cancer Recurrence If I Have Had A Mastectomy?

Yes. You are still at risk of breast cancer recurrence if you have had a bilateral mastectomy (surgical removal of both breasts). Undergoing a bilateral mastectomy drastically reduces your chances of local or contralateral breast cancer recurrence as almost all of the breast tissue has been removed. However, there is still a chance that residual breast tissue or cancer cells could recur on the chest wall.

If you have had a single mastectomy (surgical removal of one breast), you are still at risk of developing cancer in the breast that remains.

It must be noted that having a mastectomy or bi-lateral mastectomy does not reduce your risk of developing cancer in other parts of your body (distant recurrence).

How Can I Prevent Breast Cancer Recurrence?

There is no definitive way to prevent breast cancer from coming back. However, treatments such as surgery, chemotherapy, radiotherapy, targeted therapy (eg trastuzumab for HER2-positive breast cancer) and/or hormone therapy (for hormone receptor positive breast cancer) do reduce the risk of recurrence, depending on the type and stage of the cancer. These can be discussed with your treatment team.

Understanding the risk factors for breast cancer recurrence and participating in regular breast screening through BreastScreen in Australia and BreastScreen Aotearoa in New Zealand can help to pick up any breast changes. Discussion with your healthcare team can help to catch any changes or abnormalities early and act on them.

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ASCO 2020: BREAST CANCER RESEARCH SUMMARY

Read our summary of the key breast cancer clinical trials research presented at 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

American Society of Clinical Oncology 2020

The American Society of Clinical Oncology (ASCO) congress is the largest cancer conference in the world, bringing together the world’s most reputable cancer researchers, patient advocates and industry professionals, including those from Breast Cancer Trials, to discuss the latest advancements in cancer treatments, clinical trials research and cancer care.

This year, due to COVID-19 restrictions, the conference went online, with delegates logging in at all hours of the day around the world to attend sessions and lectures.

We have provided a summary of the key breast cancer clinical trials research presented:

KEYNOTE355 Clinical Trial Shows Positive Survival Data For Metastatic Triple Negative Breast Cancer

The KEYNOTE355 clinical trial was a phase three trial that evaluated an immunotherapy drug (pembrolizumab) in combination with (one of three) chemotherapy drug regimens, compared to those chemotherapy drugs alone.

This trial was open to patients with inoperable locally recurrent or metastatic triple negative breast cancer. This means the patients’ cancer has come back after treatment or has spread to other parts of the body and is unable to be removed in an operation.

Results presented at ASCO 2020 show that in patients with programmed cell death ligand (PD-L1) positive tumours with a combined positive score (CPS) equal to or more than 10, the immunotherapy plus chemotherapy treatment led to a statistically significant and clinically meaningful improvement in the amount of time patients lived without progression of their cancer.

This combination of treatment reduced the risk of disease progression or death by 35% and improved the progression-free survival to an average of 9.7 months compared to the 5.6 months for patients receiving only chemotherapy. There were some additional, manageable, immune related side effects seen with pembrolizumab.

The researchers and clinicians who worked on this trial believe that if approved, this new treatment combination could provide a new option for first-line treatment to certain patients with hard-to-treat triple-negative breast cancer.

Should The Primary Breast Cancer Be Removed In Patients Who Have Distant Metastases At The Time Of Diagnosis?

This is a question that patients and doctors frequently discuss in the clinic. Women who present with a new diagnosis of breast cancer that is already at an advanced stage (stage IV) face the question about whether surgery and radiation to the tumour of the breast (local therapy) will prolong survival compared to the traditional treatment of systemic treatment (chemotherapy or endocrine therapy) alone. The question comes down to concern about whether the primary cancer contributes to further progression of distant disease.

Data from the E2108 randomised phase three trial, presented at ASCO 2020, show that the survival experience of the two treatments was the same. Patients all started with systemic therapy, and those who had stable or responding disease were then randomised to receive surgery to the breast primary, followed by ongoing systemic therapy, or to ongoing systemic therapy alone.

Those patients who received local therapy did not survive for any longer than those who did not. It shows that surgery and radiation should not be offered to these patients with the expectation of improved survival. There may still be specific situations where surgery and/or radiotherapy to the breast may be worthwhile for patients with metastatic breast cancer, particularly if it is causing localised symptoms that are not controlled by systemic therapy. In addition, quality of life was worse in the patients who had surgery, despite having less locoregional progression.

Improved Survival For Patients With HER2 Positive Breast Cancer With Brain Metastases

Results of the HER2CLIMB clinical trial were presented at ASCO2020 showed remarkable results for patients with HER2 positive breast cancer with brain metastases. This type of cancer is often difficult to control when it has spread to the brain, resulting in short survival times.

The HER2CLIMB clinical trial was a randomised phase 2 trial which evaluated the addition of an oral drug (tucatinib) to treatment with Capecitabine and trastuzumab in patients with advanced HER2+ breast cancer that had spread to other parts of the body. The overall results have already been published, showing tucatinib prolongs survival in patients with metastatic HER2 positive breast cancer. The results presented at ASCO2020 focused on patients whose breast cancer had metastasised to the brain.

These results showed an overall survival benefit in this group of patients, which is around 50% of all HER2 positive metastatic breast cancer. The investigators found that in patients with heavily pre-treated, HER2 positive metastatic breast cancer with brain metastasis, the addition of the drug tucatinib to the combination of trastuzumab and capecitabine doubled the intracranial overall response rate, reduced the risk of intracranial progression or death by two-thirds and reduced the risk of death by half. It was also effective for patients without brain metastases.

Trastuzumab Does Not Reduce The Risk Of Recurrence For Women With HER2-Positive DCIS

Trastuzumab, one of the drugs used in the HER2CLIMB trial discussed above, was also used in the NSABP B-43 clinical trial. Trastuzumab is an established drug that reduces recurrence and prolongs disease control in early stage and metastatic HER2 positive invasive breast cancer, respectively.

The aim of this clinical trial was to see if the addition of trastuzumab to radiotherapy would reduce the pre-cancerous (DCIS) or invasive breast cancer recurrence rate for women who have had surgical removal of HER2 positive ductal carcinoma in situ (DCIS). The investigators hoped it would reduce the rate of recurrence by at least 36%, however results presented at ASCO 2020 showed it did not reach this threshold.

BYLIEVE Results Show Treatment Combination Improves Progression Free Survival For Patients With Metastatic ER-Positive, PIK3CA Mutant Breast Cancer

PIK3CA mutations are found in the tumours of approximately 40% of patients with hormone receptor-positive, HER2-negative advanced breast cancer, and is associated with treatment resistance and poor outcomes. The BYLIEVE clinical trial treated patients with metastatic hormone receptor-positive, PIK3CA mutant breast cancer with the combination of alpelisib, an alpha-specific PI3K inhibitor, and fulvestrant after prior aromatase inhibitor and CDK4/6 inhibitor treatment.

The results, presented at ASCO 2020, showed that the trial met its primary objective, with 50% of patients alive and progression free at six months. Some toxicity was identified (diarrhoea, hyperglycaemia, nausea, rash), but discontinuation due to toxicity was low, suggesting that it is manageable.

This trial result is of great interest to Breast Cancer Trials as the CAPTURE clinical trial, due to open in late 2020, will use the same combination of alpelisib and fulvestrant in patients with hormone receptor-positive HER2-negative advanced breast cancer who have a PIK3CA mutation in their blood, according to testing of circulating DNA.

While BYLIEVE was a single-arm trial, the CAPTURE trial will compare this treatment to capecitabine, which is a currently used treatment option. Such comparative trial designs are the accepted standard for moving new medications or combinations towards routine clinical use.

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ESMO 2020 BREAST CANCER VIRTUAL MEETING SUMMARY

Read our summary of some of the key breast cancer research presented at this year’s ESMO 2020.

European Society of Medical Oncology 2020

Every year the European Society of Medical Oncology (ESMO) hosts a multidisciplinary meeting in Europe, bringing together the world’s best cancer researchers to present on the latest in breast cancer research and treatments and to help design the next generation of clinical trials.

This year due to COVID-19 restrictions the meeting went virtual, with delegates logging on from all over the world to the ESMO 2020 Breast Cancer Virtual Meeting. ESMO 2020 is a congress designed for researchers and clinicians who have a specific interest in innovation (including translational research, new agents, molecular and functional diagnostics, biomarkers and cutting-edge research applications in the clinical setting) and care.

We have provided a summary of some of the key research presented at this year’s ESMO 2020.

Immunotherapy Benefit In Metastatic Breast Cancer

Two novel biomarkers (which are a way to measure what is happening in a cell or organism at any given moment) have been found to be connected with improved outcomes in those with metastatic breast cancer. It is hoped these biomarkers will help identify which patients will benefit most from immunotherapy treatments, according to exploratory studies reported at ESMO 2020.

Previous studies have shown that not every patient with metastatic breast cancer will benefit from immunotherapy treatments. Immunotherapy is a type of cancer treatment which aids the body’s immune system to fight cancer cells. Trials have focussed on patients with triple negative breast cancer and more recently HER2-positive breast cancer. However, these traditional biomarkers have not been specific enough.

To explore new potential biomarkers for immunotherapy in advanced breast cancer, researchers assessed the predictive value of copy number alteration (CNA) for the PDL1 gene (a biomarker), which measures whether the gene number has decreased, remained the same or increased. They measured CNA values in tumour tissue collected from 126 patients with metastatic breast cancer taking part in the SAFIR-IMMUNO study, the first randomised trial comparing immunotherapy using durvalumab, to maintenance chemotherapy in this setting.

The study found that nearly one in four patients had a copy gain or amplification of the PDL1 gene. This exploratory translational analysis suggested a higher efficacy of durvalumab as maintenance treatment for patients with PDL1 copy gain or amplification. Further research is needed, but the study authors suggest that this could help to identify metastatic patients that immunotherapy could benefit.

The second potential immunotherapy biomarker involved a different method of PD-L1 measurement, the combined positive score (CPS). This may also predict for increased benefit with immunotherapy.

Breast Cancer Trials currently has one immunotherapy trial open to metastatic breast cancer patients.

You can read more about the DIAmOND clinical trial here.

The Drug Trastuzumab Deruxtecan Shows Promise For Metastatic HER-2 Positive Breast Cancer

Trastuzumab deruxtecan is a new type of drug called an antibody-drug conjugate, that combines a targeted therapy with a chemotherapy payload directed only at the cells that exhibit a specific signal, in this case, HER2. A trial using this drug has shown benefits in patients with HER-2 positive metastatic breast cancer who have already received previous treatments.

In a study of 184 patients who had already undergone an average of six previous treatments, 60% of patients had a positive response to the drug, resulting in the average duration of progression free survival being around 16 months.

This is impressive, because typically very few tumours would respond to treatment after so many other treatments have already failed.

While further study is required to confirm the efficiency of this drug in a larger patient population, this result is positive for those with metastatic HER-2 positive breast cancer.

Read the full study: Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer Published December 11, 2019

Supportive Care and Physical Activity Underutilised To Help Cancer Related Fatigue

Cancer related fatigue is common for those who have received breast cancer treatment and can prevent patients from returning to life as they lived before their diagnosis. A study presented at ESMO 2020 has found that this fatigue may be due to early breast cancer patients not adhering to the recommended guidelines of physical activity.

The study found patients who reported severe levels of fatigue were less like than those with non-severe symptoms to have followed physical activity guidelines for cancer patients. The study’s authors said the take-away from these results is that patients need to be encouraged to stay active and understand that it is physical activity and not rest which will help them to overcome fatigue.

In the patient population studied, it was also found that the uptake of supportive services was low, with only one out of 10 women consulting a psychologist.

This study shows that the strategies patients adopt to help manage side effects like fatigue are strongly connected to the type and intensity of their fatigue. Ideally, people with a history of cancer should aim towards 30 minutes per day, five days per week of moderately strenuous physical activity (or more).

This may require support from health professionals and accredited exercise physiologists. The authors state that even though physical activity has been proven to reduce cancer related fatigue, it needs to form part of a more holistic treatment plan that includes access to other support services like a psychologist.

You can read more about the importance of getting psychological help during your cancer diagnosis here.

Circulating Tumour DNA Is Emerging As An Important Aspect Of Breast Cancer Monitoring And Prediction

Circulating tumour DNA is found in the blood and refers to the DNA that comes from cancerous cells and tumours. As a cancer grows, cancer cells die and are replaced by new ones. The dead cells get broken down and their contents, including DNA, go into the bloodstream. These very small pieces of DNA are called circulating tumour DNA (ctDNA).

Circulating tumour DNA was identified at ESMO 2020 to be of increasing research interest. This is because circulating tumour DNA can be used in detecting and diagnosis a tumour, guiding tumour-specific treatment, monitoring treatment and monitoring patients in remission.

Breast Cancer Trials will open the CAPTURE clinical trial this year, which uses a blood test for circulating tumour DNA to detect if a patient has the PIKC3A gene mutation. This mutation occurs in 35-40% of oestrogen receptor positive (ER+) breast cancer and may make tumours more sensitive to treatments such as alpelisib that target the PI3K pathway.

The study aims to find out if treatment with alpelisib plus fulvestrant increases survival without cancer progression compared to capecitabine in women and men with oestrogen receptor positive (ER+), HER2-negative advanced breast cancer who have a PIKC3A mutation identified in circulating tumour DNA (ctDNA).

Other Trial Results Presented At The ESMO Congress

  • KATHERINE trial: post-neoadjuvant TDM-1 is effective, even if the tumour converts from HER2-positive at pre-therapy biopsy to HER2-negative at surgery.
  • PALOMA-3: patients have prolonged progression-free survival on their next line of therapy after palbociclib and fulvestrant.
  • Tumour infiltrating lymphocytes on tumour biopsy and immunoscore predict for pathological complete response in patients with operable breast cancer treated with neoadjuvant immunotherapy.
  • Another mouthful – Ladiratuzumab Vedotin! This time an antibody drug conjugate (like TDM-1) for triple negative breast cancer (TNBC). This early phase trial demonstrated a 35% response rate in the overall trial population, and 69% in de novo metastatic TNBC.
  • Window-of-opportunity trials, where patients are given a short duration (eg two weeks) of chemo- or endocrine therapy with serial biopsies, might be of increasing interest, as presented by an eminent cancer researcher at an educational session during the meeting.
  • Tucatinib (HER2Climb) in heavily pre-treated metastatic HER2-positive breast cancer prolongs progression-free and overall survival even in the difficult to treat, poor prognosis group with brain metastases.

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LIFE AS A BREAST CANCER SURVIVOR DURING COVID-19

Although life may feel like it is beginning to return to normal for some, there are pockets of our society who still need to remain extra vigilant and cannot relax back into this new normal.

Rebecca’s Experience During the COVID-19 Pandemic

Although life may feel like it is beginning to return to normal for some with COVID-19 restrictions beginning to lift, there are pockets of our society who still need to remain extra vigilant and cannot relax back into this new normal. This includes those who are immunocompromised, like breast cancer patients.

Rebecca Angus is a member of the Breast Cancer Trials Consumer Advisory Panel (CAP).

CAP members use their experience of breast cancer to provide input and insight into Breast Cancer Trials research, ensuring a consumer perspective is provided from the very early planning stage of clinical trials.

In this Breast Cancer Trials blog, Rebecca writes about why it is important to still remain safe and socially distant for those who are immunocompromised, how her breast cancer experience has prepared her for COVID-19 and what it is like to work in healthcare during this time.

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It has been two years since my diagnosis and the commencement of breast cancer treatment. Regardless of the COVID-19 pandemic, we are celebrating my breast cancer survival and life.

Today I am at home, practising social distancing and watching my son play in the backyard. This morning I went to visit my general practitioner for my flu vaccine and monthly Zoladex injection. My annual scans are due in a few weeks; managing breast cancer does not stop during the COVID-19 pandemic.

I am currently working in healthcare as a full-time Podiatrist and making most of my precious moments at home with my family. Trying to stay healthy and exercising regularly. My health is still and always will be at the forefront of my mind.

For those with chronic illness, COVID-19 impacts on our daily lives. I honestly cannot imagine how challenging it would be at present for those newly diagnosed with breast cancer, enduring chemotherapy, immunotherapy, or participating in clinical trials.

COVID-19 has reminded me of my health vulnerabilities. While no longer undergoing chemotherapy, radiation treatment, episodes of hospitalisation and neutropenia, I still do not want to test the waters with contracting COVID-19. This human body has lived through an enormous amount of treatment!

Working in an essential healthcare service during COVID-19 pandemic means I have face to face exposure to patients on a routine basis. This will continue until my oncologist instructs me that it is unsafe to do so.

A breast cancer diagnosis and treatments have adverse financial effects on patients. At present, I am trying to balance my health with my financial responsibilities. Hoping that it will not affect our financial stability as it has previously done in the past.

My social distancing measures include driving to work and avoiding public transport. My son is dropped off to his early learning centre at the door. I bring my lunch from home and do not leave the office until I go home. At work, we have been minimising our contact with patients when appropriate to do so. As soon as the family arrives home, we shower and change our clothes.

Practising infection control and hand hygiene has always been a big part of my work life and staying healthy during breast cancer treatment. Cleaning and disinfecting surfaces at home and work regularly. At work, I wear N95 masks, eye protection, gloves and gown. Washing my hands regularly and encouraging anyone I come into contact with to wash their hands.

This includes washing hands with soap and water more frequently, and for at least 20 seconds.

It is better to use soap and water at home and use alcohol-based hand sanitizer when you are mobile. It is also important to moisturise your skin daily, especially those women on breast cancer treatment or who have been affected by lymphoedema. I also avoid touching my face at work, in public or at home.

Breast cancer patients and those on chemotherapy practice social distancing and isolation as a standard precaution. So, adjusting to the COVID -19 pandemic may be a relatively smooth transition. My family have been adopting some of our breast cancer treatment rituals again.

When attending appointments, we call the facility ahead to make sure that we are practising social distancing or opt for telehealth consultations when appropriate. We do not wait in doctors waiting rooms.

COVID-19 has separated individuals priorities in life. While the general public was stockpiling toilet paper, flour and rice at the shops. The first thought that came to me was: How is this going to impact my healthcare and the life-saving medication, which assists in preventing re-occurrence of breast cancer? Will I be able to continue to access the Neratinib medication program?

Breast cancer has certainly put what is essential in life into perspective!

At home, we have been trying to keep space between ourselves and others, limiting our exposure to people and avoid any unnecessary travel. All our food, clothing and other supplies are purchased online and delivered to home. Otherwise, my husband picks up supplies.

Self-isolation and social distancing can get lonely at times, especially when your undergoing chemotherapy.

Your family and friends are the foundation of your support network, and with the social distancing rules, it can make it difficult at times. Trying to find fun ways to interact with your loved ones is essential.

Social media, facetime or zoom chat your family and friends. Make sure you discuss your mental health concerns with your doctor, psychologist or access free online evidence-based tools such as Finding My Way or BCNA My Journey.

Keep your routine as best as possible, including getting exposure to plenty of fresh air and exercise. You can also access prescribed exercise physiology and physiotherapy apps. These can be designed by your health professional to be completed at home, under a Medicare plan. For further information, discuss this with your general practitioner.

Yoga and meditation DVD’s/ online resources were tools that I used during my treatment to assist in managing my mental health. I plan to continue to practise them during COVID-19.

Breast Cancer Trials needs to continue their life-saving work and clinical trials into breast cancer throughout COVID-19. I am sending love and support to those involved in clinical trials and oncology care. The true health care heroes are our researchers, doctors and nurses.

To the trial participants and their families. My thoughts are with you; please stay safe. Lastly, please stay home for breast cancer patients and their families.

Our research is still continuing during COVID-19.

You can help support our life-saving research during this difficult time here.

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Ms Rebecca Angus

Rebecca Angus is a Senior Podiatrist working in Sydney and is a member of the Breast Cancer Trials Consumer Advisory Panel. She was diagnosed with breast cancer in 2018.

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WHAT HAPPENS DURING A CLINICAL TRIAL?

Clinical trials are an important part of our health system and we answer some frequently asked questions about what happens during a clinical trial.

What Is A Clinical Trial?

Clinical trials are an important part of our health system and are necessary to find out if new treatments are more effective than those currently accepted as the best available standard of care. They are designed to answer a scientific question and compare whether a new treatment is better than the current treatment. In fact, the current treatments that are saving lives today are typically only available because clinical trials have shown that they are beneficial.

All new breast cancer treatments or prevention strategies must be rigorously tested through the clinical trials process before they are made widely available to the community. This includes chemotherapy and hormone treatments to prevent recurrence and save lives, mammograms and breast cancer surgeries.

Who Participates In A Clinical Trial?

People who participate in a clinical trial volunteer to do so. In terms of breast cancer clinical trials, participants have been diagnosed with breast cancer or in regard to prevention trials, are at higher than average risk of being diagnosed with breast cancer.

Participants in any clinical trials need to understand what is going to be involved. This is the process of informed consent, before signing onto a trial. The treating physician and clinical trial coordinator will go through this information with the potential participant. This will include an explanation of the trial protocol and provision of written participant information and consent forms. They will discuss the trials aims, potential side effects and what kind of trial it is. Potential participants are given time to read about it, ask questions, discuss with their friends, family and other health professionals before deciding to enter the trial.

Is It Safe To Participate In A Clinical Trial?

Yes.

The health and safety of clinical trial participants is the first priority in the trials process. By the time a treatment is used in a clinical trial, it has already gone through exhaustive testing. It will then be used very carefully in a trial with a small number of volunteers to ensure safety, before larger trials are done to find out if it effective against cancer. These trials are designed by doctors and researchers who are highly respected leaders in their field, with the support of rigorous scientific evidence.

As with any medical treatment, there is the possibility of side effects. However, the treatments are developed and tested so that the doses used are not expected to lead to excessive side effects, and that those possible side effects have treatment strategies available. The potential side effects are explained to the person before they choose to enter into the trial, to ensure that they are making an informed decision.

The research is overseen by independent people who are not involved in the initial trial development process. This is done by checking through the clinical trial protocol, which outlines the reason for doing the study, who may participate, the treatments and tests involved, when these will be done and why. This independent panel of scientists, medical professionals and consumers is called an ethics committee. The progress of the clinical trial and the safety of clinical trial participants is carefully reviewed and monitored by an Independent Data and Safety Monitoring Committee and by the ethics committee responsible for approving the clinical trial.

Before joining a clinical trial, potential participants must understand why the clinical trial is being conducted, the potential risks and benefits and what their involvement would include. The decision to participate is made on the basis of information provided to the patient by their treating doctor.

A trial participant can choose to remove themselves from the clinical trial at any time. A patient’s treating doctor can also choose to take the participant off the trial if they believe they are having an adverse reaction to a treatment. If a treatment or intervention being tested in a clinical trial is showing no benefit to participants, then the researchers conducting the study will decide if all participants should be taken off the treatment or intervention being trialled.

What Phases Are Involved During A Clinical Trial?

Clinical trials are generally conducted in four phases. Each phase is designed to answer certain scientific questions.

Phase One Clinical Trial

Phase 1 clinical trials are conducted to test a new biomedical intervention (treatment) for the first time in a small group of people (around 20 to 50 people) to evaluate the safety and side effects of the new treatment or intervention. Phase 1 trials are not usually randomised.

Phase Two Clinical Trial

If the treatment or intervention is proven successful in phase one, it is moved to a phase 2 study and tested in a larger group of people (generally several hundred) to give an indication of how effective it is and to further evaluate its safety.

Phase Three Clinical Trial

Phase 3 clinical trials compare new treatments with the best currently available treatment (standard treatment). Phase 3 clinical trials study the efficacy of a treatment or intervention in large groups of people (several hundred to several thousand). They look at which treatments work best for the disease, how the treatment affects quality of life and learns more about side effects. A phase 3 clinical trial could compare the standard treatment with a new treatment, a different dose of the same treatment or a different way of giving the same treatment. These are usually randomised, meaning that participants are allocated to one of two or more treatment options at random, and neither they or their doctors get to choose which treatment. Determined This helps to remove any biases that could lead to false conclusions being made about the effectiveness of the new treatment. Importantly, with this type of trial, participants are given the current standard of care at a minimum, and the new treatment is hoped to be better than that standard care (or at the minimum, no worse).

Phase Four Clinical Trial

A phase 4 clinical trial is conducted after the new treatment or intervention has been approved and entered routine clinical practice. A phase 4 clinical trial aims to learn more about the side effects and safety of the new treatment, the long-term risks and benefits of the new treatment and how effective the treatment is when used in the general population over a longer period of time.

How Long Do Clinical Trials Take?

The length of a clinical trial is dependent on what kind of trial and treatment is being tested. This means each clinical trial timeline is different and we cannot say definitively how long each phase of a clinical trial will last. If you are considering signing on to a clinical trial, this information will be communicated to you by your treating doctor and the clinical trial coordinator. The following information is intended only as a guide and may not be relevant to your individual situation:

Phase 1 trials may last less than a year as these trials are testing in small groups and evaluate the safety of a new treatment or drug. However, if the patient is benefiting from the treatment, the patient may continue on the clinical trial and treatment for longer. This is dependent on individual circumstances.

Phase 2 trials may be longer than phase 1 trials as there are more participants, which means recruitment may take longer. Though recruitment may take longer, patients may be on the treatment for a similar time to those on a phase one trial.

Phase 3 trials, the most common phase trials, may take longer than phase 1 and 2 clinical trials, but the duration depends on the size of the clinical trial, what stage of cancer is being treated and what the determined end points for the clinical trials. For example, the large adjuvant clinical trials SOFT and TEXT have been going on for around a decade, with follow-up still occurring. This does not mean patients are still receiving active treatment, but it does mean researchers are still examining the benefit of the treatment patients received through follow-up consultations.

Phase 4 trials can last for a few years to more than a decade as it is testing the long-term risks and benefits of a new treatment in a larger population, over a longer period of time.

What Happens When A Clinical Trial Ends?

When a clinical trial has reached its determined end point, the researchers involved in the study will evaluate all the information collected. An analysis is also usually conducted during the clinical trial. All this information collected during and post- trial will help to determine if the treatment or intervention should continue to the next phase of the clinical trial, or if the treatment or intervention should be approved for use in the clinic by the relevant health authorities. Once a new treatment has been proven in a clinical trial, the addition of this treatment to the Pharmaceutical Benefits Scheme (PBS) in Australia and PHARMAC in New Zealand, is a separate process and can take several years.

There are a lot of factors that determine how long it will take for a safe and effective treatment to be approved for use in the clinic. Larger trials that have had thousands of participants will take longer to evaluate than smaller trials. This can take a number of years.

Participants are also usually involved in follow-up for years after their involvement in the active treatment part of a clinical trial. This means they are monitored for many years after their active involvement has finished, including when they have finished taking the treatment tested in the clinical trial. This follow-up could include filling in a survey each year or receiving check-ups with your treating doctor. This helps researchers study the long-term effects and efficiency of the treatment or intervention studied.

If you have participated in a clinical trial, the researchers should make the results of the study available to you directly when they become available. Results are generally presented in reports or published in scientific journals.

Can I Participate In Two Clinical Trials At Once?

Generally, researchers prefer clinical trial participants to be involved in only one clinical trial at a time. This is so they can clearly attribute the risks and benefits of each treatment or intervention to the clinical trial. There are exceptions; however, clinical trial participants can be involved in a therapeutic trial and a tumour banking trial, a quality of life or lifestyle intervention trial simultaneously. Your treating doctor will advise on what trials you can participate in.

Can I Discuss The Clinical Trial With My Family And Friends?

Yes!

Your doctor and clinical trial team will encourage you to discuss your participation in clinical trials with trusted loved ones so you can feel confident in your choice to participate. Additionally, the more people who are aware of and understand clinical trials the better. This helps to increase participation in clinical trials which helps to further breast cancer research and help to find new and better treatments and prevention strategies for the disease. You may also wish to discuss the trial with other health professionals such as your GP prior to participation.

Will My Details Be Published To The Public?

No.

Patient privacy is of the utmost importance is the clinical trials process. Once you consent to take part in a clinical trial, your information will form part of the clinical trials records and be processed in line with the applicable laws that control clinical trials. This means that identifying information such as name, date of birth and address are removed from your information, and replaced with a code, so that the researchers analysing the information cannot identify you as an individual. In any case, the trial information is generally only meaningful when it is analysed as a group, not from any one participant on their own.

When participating in a Breast Cancer Trials clinical trial, your confidential health information will only be accessed by people involved in the clinical trial, including health care professionals and Breast Cancer Trials research staff who are all dedicated to upholding the rights of trial participants to privacy. Any identifying details are removed by your treating doctor or clinical trial coordinator prior to the data being send to the data repository, for example the Breast Cancer Trials database.

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HOW OUR RESEARCHERS ARE RESPONDING TO COVID-19

Professor Fran Boyle AM and Associate Professor Nicholas Wilcken discuss how their institutions and teams have responded to the COVID-19 pandemic. They discuss how some changes have been positive, how their patients have reacted to this new environment, and give a BCT research update.

Responding To COVID-19

In this Breast Cancer Trials (BCT) members podcast, Professor Fran Boyle AM and Associate Professor Nicholas Wilcken discuss how those involved in breast cancer care and treatment have responded to the COVID-19 pandemic.

Professor Fran Boyle is a Medical Oncologist at North Sydney’s Mater Hospital, where she is the Director of the Patricia Ritchie Centre for Cancer Care and Research, and Professor of Medical Oncology at the University of Sydney. Professor Boyle has been involved in breast cancer clinical trials research for the past 20 years. She has chaired the BCT Board and is a current member of the BCT Scientific Advisory Committee.

Associate Professor Nicholas Wilcken is the Director of Medical Oncology at the Crown Princess Mary Cancer Centre Westmead, Senior Staff Specialist at Nepean Hospital and Associate Professor of Medicine at the University of Sydney. Associate Professor Wilcken was elected to the BCT Board of Directors in July 2016. He was the Chair of the BCT’s Scientific Advisory Committee from 2011 to March 2017.

Listen to the podcast

A Podcast about breast cancer and COVID-19 between Professor Fran Boyle and Associate Professor Nicholas Wilcken.

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Help us to change lives through breast cancer clinical trials research

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Professor Fran Boyle

Professor Fran Boyle is a Medical Oncologist at North Sydney’s Mater Hospital, where she is the Director of the Patricia Ritchie Centre for Cancer Care and Research, and Professor of Medical Oncology at the University of Sydney.

Associate Professor Nicholas Wilcken

Associate Professor Nicholas Wilcken is the Director of Medical Oncology at the Crown Princess Mary Cancer Centre Westmead, Senior Staff Specialist at Nepean Hospital and Associate Professor of Medicine at the University of Sydney.

Latest Articles

can a breast cyst turn out to be cancer?
triple-positive breast cancer