What is Finding My Way?

Finding My Way is an online coping program for individuals who have been diagnosed with cancer.

The program is designed to support people through their cancer diagnosis, as well as help to provide strategies to live well despite this diagnosis.

Associate Professor Lisa Beatty is a Clinical Psychologist at Flinders University. She was a guest speaker at the 2022 BBCT ASM where we asked her to explain her talk discussing the “Finding My Way” program and how it was initiated.

“So, ‘Finding My Way’ is an online coping program for people who have been diagnosed with cancer. We’ve got two different versions. There’s one that’s designed for people with early-stage cancers where the intention is to cure their cancer, and we’ve got a new version that we’re just about to start trialling called ‘Finding My Way Advanced’, which is designed for women with metastatic breast cancer.”

“The program is designed to help support people with their most commonly experienced issues and concerns that arise after diagnosis and through treatment. And really, it’s ultimately aimed at helping to provide strategies to live well with their cancer, especially for ‘Finding My Way Advanced’, where it’s for women where there’s no end date for their treatment, they’ll be continuing to receive treatment ongoing.”

“So, it’s around maximising quality of life and giving strategies to do that while they’re going through their treatment. ‘Finding My Way Advanced’ is actually aimed at any woman at any point after they’ve been diagnosed. It’s not just for those recently diagnosed. And those who can read English fluently to be able to understand the program, as we haven’t been able to translate it yet in this current format.”

“It’s not just from the point of diagnosis, we do cover some of the issues relating to navigating healthcare that might come up at diagnosis. But we also cover things like managing your physical symptoms and side effects and coping with some of the unique challenges of knowing your illness won’t be cured. It will progress potentially at some point, but you might be stable for a long time.”

“So, managing those issues, coping emotionally, coping with changes that you might experience with your social support and how to support your loved ones as well. So, there’s a range of topics and it really is aimed at any female that’s been diagnosed at 18 and above with metastatic breast cancer.”

How Important is it to Provide an Online Support Service?

“Yes, so that’s one of the main reasons why we went to developing these programs online is because we know that clinically significant distress, so depression, anxiety, distress after diagnosis is very prevalent. So, we know that approximately 40% of women will experience that, but of those only 29% of women, when they’re offered a service face-to-face, will actually take it up.”

“There’s lots of barriers to accessing your traditional mental health clinicians or services where they are available. And some of those barriers are for people who live in rural or remote areas, where it’s a lot harder to attend. And there might not be services available out there for those who might have other responsibilities and are juggling their personal lives, work, and other responsibilities. Trying to fit those face-to-face appointments can be really challenging.”

“So, for a range of reasons we had already developed this program to be online and that was before Covid-19 was here.”

“And now I think the whole pandemic made everyone realise how important it was that we have these online options to be able to continue providing some sort of service for those situations where no one can attend in person. And we also know that currently, or over time people are using the internet anyway to look up Dr Google, or look up information and support anyway. So it’s about trying to make sure we provide credible, reliable, evidence-based information.”

“So that’s sort of how it came about and I guess the one thing I can say is that at times we might be experiencing a little bit of zoom fatigue or online fatigue at this point in the pandemic, but it’s still here to stay. And I think people are feeling far more aware of online resources and are more familiar with them and how to use them.”

“So, we’re overcoming some of those early technology barriers as well. I think probably because of Covid-19.”

Feedback From ‘Finding My Way’ Users

“So far, we’ve done a few different versions or tests of the program for ‘Finding My Way Advanced’ for women and what we did in the first stage of testing was to basically sit side by side with the female with metastatic breast cancer, while she was navigating her way through it. We wanted to see whether there were any issues or glitches or any points of confusion that she would change.”

“So, we had the researchers sitting alongside her and that’s called a ‘think aloud’ process where we are trying to voice what was going through her mind while she was trying to navigate it.”

“So, we were able to get some really deep feedback from women from doing that, who overwhelmingly said what a positive and helpful resource it was and that it really did help them cope while they were going through this treatment.”

“We then went on to the second stage of testing the program, where we gave it to women as a randomised control trial.  So half the women received the program and the other half received the Breast Cancer Network Australia ‘Hope and Hurdles’ kit, which is a great resource.”

“We then got feedback from women in that study as well, and again it was very positive feedback around how helpful and supportive it is. And at times there can be some challenging content in there. We do provide information about how to cope when you find out that your illness might have progressed, planning ahead, what to do, and how to prepare yourself a little bit.”

Associate Professor Beatty’s Hope for the Future

“We’ve just received funding from Cancer Australia to do a big national multi-site study. Now that we know that we’ve got the program in its best possible format and that is usable and the early indicators are promising, we’re now going to roll it out across the country at various hospitals.”

“We will be recruiting 370 women for this study to see whether it really does lead to improvements in quality of life and whether it does help to reduce distress. And then after that, we’re working in close partnership with Breast Cancer Network Australia who have committed to make the program available afterwards, should it be safe and helpful, which we’re confident it will but we have to go through the trial process first to demonstrate that.”

The BRCA-P Prevention Study

At least one in 400 women in the developed world carries the hereditary BRCA1 gene mutation. This mutation is associated with approximately 70% risk of developing breast cancer and 40% risk of developing ovarian cancer over the course of a lifetime. The BRCA-P clinical trial is a preventative trial which is testing the effectiveness of a drug called denosumab in preventing breast cancer for these women.

Dr Christine Muttiah is a medical oncologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital and is also working in the breast cancer lab at the Walter and Eliza Hall Institute of Medical Research in Melbourne.

As part of a Clinical Fellowship project with Breast Cancer Trials, Dr Christine Muttiah is aiming to assist in the clinical conduct of the BRCA-P study in the hopes to increase recruitment across all 14 Breast Cancer Trials BRCA-P sites.

“So, I have two projects as part of the Breast Cancer Trials Clinical Fellowship. The one I’m working on at the moment is related to the BRCA-P prevention study. So that study is an international study looking at the use of a medication to prevent breast cancer forming in women who have a gene mutation.”

“The research came from the lab here in WEHI to establish that international study. So, it’s really exciting to be part of that at Royal Melbourne and Peter McCallum Cancer Centre. But my project is focused on helping Breast Cancer Trials to increase recruitment to the study at all sites across Australia, and sort of be a central point of contact for any women who might be interested in the study.”

The Importance of the BRCA-P Trial in Opening Up a New Treatment Opportunity

“Generally, women who have been found to carry a BRCA1 mutation are seen in surveillance clinics. They might see a breast surgeon or a breast physician where they would get examinations and breast imaging every year, and also have discussions about how to reduce their risk of developing breast cancer.”

“So currently the most effective way of reducing the risk of breast cancer is to have a prophylactic mastectomy, but obviously that’s not for everyone. So that’s where discussions about prevention such as this clinical trial is important. And those discussions generally happen in very busy clinics.”

“So my role I guess is to take some of that burden off local clinicians and have those discussions with women.”

The Benefits of Centralised and Accessible Recruitment

“I think the benefit of having this centralised process is that I know the study quite well and we’ve been quite successful here at the Peter MacCallum and Royal Melbourne in recruiting patients.”

“So hopefully having that discussion with one person, I guess just to find out more without having to commit should hopefully ease any anxieties people might have about the study.”

“So, for prevention studies looking at centralising recruitment might be something that helps Breast Cancer Trials in the future, particularly in studies such as this where we’re trying to recruit a large number of women to an international study. So hopefully the successes of this centralized process will give us more information about how we can reach all women in Australia and New Zealand to give them access and opportunity to be on a breast cancer trial whether it’s therapeutic or prevention.”

Being Involved in a World-First Clinical Trial

Dr Muttiah discusses the hope that women feel that they are involved in a trial that could potentially change treatment options for future generations who carry the BRCA1 gene mutation.

“Here at the Peter Mac and Royal Melbourne we have about 20 or more women who are part of the BRCA-P study. So being part of the BRCA-P study has been really important to them because unfortunately they’ve been impacted by close family members who have had cancer diagnoses due to the hereditary nature of the gene mutation.”

“For the women on the BRCA-P study, participating gives them hope that they’ll be able to hopefully change the future for their daughters, nurses, and their granddaughters. And so the women on the study are really enthusiastic about contributing to research and promoting the study.”

“I think that’s a really positive thing to hear from these women.”

How do you define a Young Women in relation to Breast Cancer?

Young women diagnosed with both early and advanced stage breast cancer, face a variety of problems unique to or accentuated by their young age. This includes career development, completing education, family planning, or parenting young children.

As part of a Clinical Fellowship project with Breast Cancer Trials, Dr Elizabeth Blackley is working on a study that involves the collection of data and the development of a registry on breast cancer incidents, treatment outcomes and quality of life metrics in young Australian women.

The aim is to help form a streamlined model of care for young women and offer various support services to help them through their diagnosis.

“For the purpose of clinical trials we define young women as younger than 45 and that’s really been because in clinical trials, we need to have such a stringent inclusion and exclusion data, so we can validate the data and the findings that are in the study.”

“In practice really what we refer to when we talk about young women is pre-menopausal women. And young women have such a unique set of challenges with breast cancer because of the stage of life they’re in at the time of diagnosis, in terms of education or career development, potentially being in new relationships, having children, wanting to have a family. It’s quite a unique role for young women that really can’t be filled by another person.”

What are the Unique Problems Faced by Young Women Diagnosed with Breast Cancer?

“So young women are often diagnosed at a stage in their life where they engage in multiple roles that can’t easily be filled by other people. So, things like parenting and motherhood, employment and career development, education. And it’s something that a lot of women struggle with balancing these things or planning for these things while undergoing treatment for breast cancer.”

“I guess from a biological perspective, there’s also a difference in young women’s breast cancers, which do tend to behave more aggressively than the same type of breast cancer in an older post-menopausal woman. They tend to be more aggressive, present at a later stage, and require more intensive treatments like chemotherapy and longer-term maintenance hormonal therapy.”

What Treatment Options are Available for Young Women?

“So, treatment for breast cancer is often intensified for younger women to combat the increased risk of their disease. This might mean they have more protracted or aggressive chemotherapy, and many years of hormonal therapy which presents higher rates of toxicity in younger women.”

“Premenopausal women with hormone receptor positive breast cancers will often require treatment with ovarian function suppression, which essentially is a treatment that induces premature menopause. So not only do women encounter the emotional symptoms of menopause, but they also run the long-term risk of premature menopause complications, things like osteoporosis and cardiovascular disease can occur.”

An Overview of Dr Blackley’s Project

Developing new research ideas and supporting the next generation of researchers is at the heart of the new Clinical Fellowship Program.

The Program is aimed at early career researchers, who have a high-level interest in clinical research and qualifications in the disciplines of medical oncology, pathology, psychology and other supportive care specialties, radiation oncology, radiology or surgery.

“So, I aim to establish a young women’s breast cancer group, which would be comprised of clinicians, adversity groups such as BCNA, Breast Cancer Trials representatives, as well as patients and carers undergoing treatment for breast cancer to try to develop or identify areas of need in young women with breast cancer.”

“In addition to this, I’m hoping to design a registry-based trial to collect prospective Australian data on breast cancer incidence, treatment, cancer and quality of life outcomes in young women, and also to help perform a needs analysis to help us determine whether gaps in cancer care for young women are.”

What Does a Streamlined Model of Care for Young Women Look Like?

“As a medical oncologist, an initial consultation with a young woman we will not just talk about the breast cancer diagnosis, the type of cancer, or the stage of the cancer. We’ll also have to focus on treatment options including chemotherapy, targeted therapies, and hormonal therapies. The potential plan and timing of surgery and radiotherapy and sequencing all these treatments together.”

“We have to cover the toxicities, the side effects, the duration, the course of treatment, but in addition we also have to discuss things like the fertility implications in a premenopausal woman who may not have started a family yet or have completed a family. And that will generally be a very time critical thing.”

“If a woman needs chemotherapy, they generally must undergo fertility preservation prior to starting, which will mean seeing a fertility specialist, usually having ovarian stimulation and the collection of eggs, and all of this is before we can even start treating their breast cancer.”

“In that initial consultation we also discuss genetic testing, particularly in young women because it is more unusual for them to develop breast cancer. There are more commonly genetic links for them. So, we’ll discuss the process of genetic testing and the implications to both their future care, their surgical options, they’re screening, but also to that of their children and relatives, all in that initial consultation.”

“The other things we will discuss often include employment and finances through a course of chemotherapy, which can be a major stress, arrangements for childcare and school-aged children, and risk of infection in treatment. They may need to discuss insertion of a central access device like a PORT, and things like scalp cooling for primary prevention of alopecia.”

“This is just sort of an array of things.”

“We know that women walk away retaining only a very small proportion of it. Part of what I see establishing a centralised or a standardised model of care would be about making this process more streamlined and having easier access to information for women going through this process, to understand that these are sort of the first steps and how to get through it.”

“Support groups and breast care nurses do an incredible job, but there’s just not enough to actually support these women going through this and it’s a very different entity to a post-menopausal woman.”

“The other part that we would like to include in this sort of model of care is the survivorship side of things. The longer-term outcomes of having had chemotherapy or breast cancer surgery, the outcomes in terms of fertility and pregnancy after breast cancer, the late toxicity risk and the psychological aspects like fear of recurrence are really very major aspects that impact on a young woman’s life.”

“I think having a standardised model of care will help to make sure that none of these aspects are neglected or missed and that it is something that all patients undergoing breast cancer at a young age can access.”

Dr Blackley’s Hope for the Future

“So, I guess we don’t have a lot of data in an Australian capacity. There’s a lot of data from America and Europe about younger women, and some of the supportive care needs and things, but we don’t really have an Australian experience. So, I guess the first step of creating a registry is really about being able to show the magnitude of the problem and how many young women we’re talking about.”

“We have very basic data through cancer registries and things, but this would be providing more detail on the types of cancer, the treatments that patients have had and it would also provide us with a pool of patients, to start looking at needs analysis and surveying patients to find out what we’re doing well and what we’re not doing well.”

“And from a needs analysis point of view, we might be able to identify something to implement. So, whether it be a central care coordinator or a particular model of care, to be able to implement that, to address some of these women’s concerns and fill some of these gaps is really important.

“By having this registry of women that we can use in this quality-of-life trial, we can actually follow them over time and establish whether the implementation of a standardised model of care actually improves their quality-of-life outcomes, improve their cancer outcomes, and improves their survivorship outcomes.”

“So, I think really collecting the data to show the magnitude of the problem is only the start, but it will enable us to tap into that database to design future clinical trials. I guess I also see it as something that would tie in with translational research, and there is quite a lot being done in Victoria at least with translational aspects of young women’s breast cancer, and looking at biology, and genomic sequencing.”

“And I see a registry and identifying these women as potentially being able to feed straight into translational clinical trials, by identifying the patients that we’re trying to target. I guess the dream is that I envision this project to be part of a much larger entity, where young women with breast cancer can all be linked into a centralised service to access clinical care coordination, and supportive care throughout their breast cancer journey.”

“And clinicians can access resources and supports caring for this very highly specialised group of younger patients. I’m aware that this is just a starting point, but I think it’s a really important one and I’m hugely grateful to Breast Cancer Trials for giving me this opportunity.”

“Young women’s breast cancer is sort of my area of passion, and while it can be a really difficult area of medicine, it’s also an immensely rewarding one where women come back many years after treatment, having progressed, made major life milestones, had babies, got married and been promoted at work and just really thrived after having breast cancer.”

“I think focusing on that and encouraging and supporting women to do so is a really important goal.”

To find out more about Breast Cancer Trials Clinical Fellowship Program, click here. 

Early Detection of Metastatic Disease

Metastatic breast cancer or cancer which has spread to other parts of the body most commonly appears in the liver, brain bones or lungs. Every metastatic breast cancer diagnosis is different and will therefore require different treatments. The aim of treating metastatic breast cancer is to control the growth and spread of the cancer, to relieve symptoms and improve or maintain quality of life.

Professor Prue Francis is a Medical Oncologist and the Clinical Head of Breast Medical Oncology at the Peter MacCallum Cancer Centre. Professor Prue Francis was a recent guest speaker at the 2022 Breast Cancer Trials Annual Scientific Meeting and her presentation was titled: Does Detecting Metastatic Disease Early Make a Difference?

“Well thus far the evidence that we have from randomised trials has not shown that detecting distant metastases early makes a difference in patient outcomes. The data we have is based on randomised trials that were done quite a long time ago.”

“They were conducted during the 1980s, early 90s and published in 1990 for two large trials, that suggest that regular scans, blood tests and X-rays did not give a longer survival for patients if they were done during follow up compared to standard follow up. This includes physical examination and mammography follow up, which would be considered routine.”

“So, the recommendations from American guidelines like ASCO, or College of Physicians in Australia, or the Medical Oncology Group, do not recommend doing routine scans and blood tests for follow up of asymptomatic patients with early breast cancer.”

“We do recommend breast imaging, a physical exam, and scans if there were symptoms and there’s research on metastatic disease primarily concentrated on improving quality of life or extending life. So, in terms of research for metastatic disease, I suppose one of our biggest goals is trying to extend life because that’s very important to patients.”

“So, if a drug is or a treatment program is compared to a current gold standard and shown to improve overall survival significantly, then that is a treatment that we will want to implement. So that’s considered a gold standard.”

Will there be a Cure for Metastatic Breast Cancer?

“I think we will have a cure perhaps not for all metastatic breast cancer, but I think for some metastatic breast cancer. In fact, I think already for some metastatic breast cancer, very selected occasional cases, I believe we probably already are curing some.”

“Those patients might be patients with metastatic HER2+ breast cancer where there are some patients that appear to go into a very long-term remission and have not relapsed.”

“So, for example, there was a trial done in patients who were getting their first line of therapy for metastatic HER2 positive breast cancer. And the patients who were treated with chemotherapy plus to HER2 targeted agents trastuzumab and pertuzumab, at 8 years there were 16% of those patients who had their disease controlled and it had not progressed. So that’s a long period of time to have your disease controlled.”

“So, I believe within those two positive patients there may be some that are cured, and I think there will be other small subsets that we will be able to find cures for. It may take a lot longer to try and find cures for all the types of metastatic breast cancer.”

New Options in HR+ Breast Cancer

“I really had fun putting together that talk and really talked about the natural history of metastatic HR+ breast cancer. It’s the most common subset in the most common cancer diagnosed in women worldwide, and our standards of care are sequential endocrine Therapy now with targeted agents.”

“We’ve made enormous advances with CDK4/6 inhibitors, with inhibitors of the PI3K pathway where many new agents are being tested. And now we have these oral selective oestrogen receptor down regulators on the horizon. But all patients will eventually develop resistance to endocrine therapy and go on to sequential single agent chemotherapy, and I think there’s concern as the CDK4/6 inhibitors move into the adjuvant setting that we will start seeing that sooner in the patients who are unfortunate enough to have endocrine resistance sooner.”

“So single agent sequential chemotherapy has the problem with lower response rates sequentially and also cumulative toxicity which really limits treatment in particular neuropathy and of course fatigue, which is part and parcel of all of our treatments. So, antibody drug conjugates are really exciting because this is a novel way, and apparently even more effective than we could’ve imagined, to deliver toxins to the cancer cell.”

“The antibody drug conjugates that are now the second plus generation have better linkers that are digested more easily in the cancer cell. And also, they have hydrophilic toxins that can leak out of the cell and kill nearby cells, that maybe don’t express the antigen on the cell surface that the antibody is targeted to as highly, but the toxins still kill the neighbouring cells.”

“So that’s called the bystander effect. And it’s an important part of these newer ADC’s along with the other things I mentioned. Then of course you need a target and so, you know, one effective way of making an antibody drug conjugate is to use trastuzumab as the backbone, and we’ve certainly seen great success and continuing remarkable success in that area, even in tumours that aren’t strictly HER2+.”

The TROPICS-02 Study Results Presented at ASCO 2022

“But first in class, novel antibody drug conjugate, sacituzumab govitecan was the subject of the Tropics-02 study that was presented at ASCO and is now in press and that is a novel antibody directed against TROP-2. And TROP-2 is an antigen that’s on most breast cancer cells and is highly expressed certainly in triple negative and HR+ cancers as data has shown. And there’s some suggestion that expression has been associated with a worse outcome and potentially resistant, so it might be something you’d want to target.”

“Sacituzumab govitecan is an antibody drug conjugate with the antibody directed to TROP-2, and then the toxin is the active metabolite of irinotecan called SN-38. So, it allows you to deliver a small amount of drug that’s highly potent directly to the cancer cell.”

“Sacituzumab govitecan after showing efficacy in a large Phase One B/2 trial in triple negative disease, improved progression free and overall survival in the Phase Three ascent trial and triple negative breast cancer, with the primary toxic being neutropenia and to a lesser degree diarrhoea. And about 50% of patients use growth factors. And now sacituzumab is more broadly approved for the treatment of metastatic triple negative breast cancer, receiving at least one line of therapy in the metastatic setting.”

“And ASCENT was positive even though patients could have received any number of lines of treatment.”

“So, the same approach was used in Tropics-02. This trial capitalized on data from a Phase One B trial, in just 54 patients, where there was a response rate of 30% and a respectable progression-free survival in hormone refractory heavily pre-treated hormone receptor positive metastatic breast cancer.”

“So, Tropics-02 targeted the same population, required at least two lines of chemotherapy for metastatic disease, but not more than four. And randomized patients to receive sacituzumab govitecan versus chemotherapy of physician choice with the primary endpoint of progression free survival by blinded independent review. And then overall survival was a secondary endpoint along with our usual safety and patient reported outcomes and response rates.”

The Design and Eligibility Criteria

“The statistical design was a hierarchical design. So, you had to have a statistical significance in each prior endpoint before you could do the next one with statistical significance. This meaning essentially that you had to have statistical significance in PFS to look at OS, and significance in OS to look at response and then patient reported outcomes. The hazard ratio that the trial was powered for was 0.7 with a two-sided P-value of 0.5. So the trial enrolled over 500 patients who had a median of three lines of prior chemotherapy for metastatic disease.”

“In order to be eligible for the trial you had to have received a CDK4/6 inhibitor and a taxane in any setting. And then these patients also you know had received a lot of prior chemotherapy, about 80% had received prior capecitabine. In the treatment of physician choice, about 50% received eribulin as the comparator chemotherapy. So, what we saw was that progression free survival was significantly prolonged in patients who received sacituzumab compared to the chemotherapy arm, and the hazard ratio was 0.66, so it exceeded our goal.”

“The median difference in PFS was 1.5 months, but the issue with looking at medians by Kaplan Meier calculation is that in the first two months, about 20% or more of the patients in both arms had progressive disease. Mainly because patients were very heavily pre-treated and had universal chemotherapy resistant disease. After that period of time, the curve separated, and stayed separated over time.”

“So, we looked at landmark analyses to try and help us understand the true benefit of sacituzumab of at 6, 9 and 12 months sacituzumab was superior to treatment of physician choice and notably at 12 months, there was a threefold improvement in the patients who are free from progression or death, who were treated with sacituzumab compared to those treated with the chemotherapy. So, it was 21 versus 7%.”

“Overall response was also increased. Although we could only do nominal P-values because the overall survival in this first interim analysis was not significantly better with sacituzumab. Numerically there was a longer overall survival but of course it really had no P-value of significance. There are three total planned analyses, and we hope to see the next analysis – the second interim analysis in the next year or shorter. It all depends on events.”

“So overall response, we looked at quality of life and global health status. Quality of life had a longer time to deterioration in patients receiving sacituzumab versus treatment of physician choice, as did fatigue. Pain was about the same and we will present more data on the quality of life at ESMO 2022.”

“So, we felt based on that data that sacituzumab govitecan was a new potential option for treatment, in patients with hormone receptor positive, heavily pre-treated metastatic breast cancer, based on all of this data.”

“We looked at safety because that’s an important consideration. And there were no new safety signals compared to the Phase Three ASCENT trial, which led to regulatory approval. Primarily neutropenia, and then to a lesser degree diarrhoea. And we also understood looking at the events in those patients that it’s very important to be proactive about treating the neutropenia with growth factors, delay in treatment, and dose reductions when appropriate, in order to avoid neutropenia complications.”

“The NCCN guidelines, so the National Comprehensive Cancer Network, updated their guidelines right after ASCO 2022 based on the data from Destiny-Breast04 that looked at trastuzumab deruxtecan in HER2-low disease 1+ or 2+ with the primary endpoint being in HR+ breast cancer. Just 58 patients had triple negative disease.”

“And then also based on Tropics-02, enlisted both as options for patients who have metastatic breast cancer who are on chemotherapy, was the eligibility or the suggested eligibility in the NCC and guidelines mirroring the trials. So heavily pre-treated HR+ disease for trastuzumab deruxtecan at least one line of prior chemotherapy and HER2-low disease confirmed by pathologic testing.”

How will this Research Benefit Patients?

“The overarching goal is to prevent metastatic disease and to cure patients with early-stage breast cancer with the least toxicity. So, you want the least acute toxicity and you really want no, if possible, long term side effects from the treatment you’ve delivered. We know we can already improve outcome for triple negative disease by being giving checkpoint inhibitors. But we also know that immunotherapy can result in long term toxicity.”

“So, we’re willing to give up a little bit of that in order to cure more patients from a very high-risk fatal disease otherwise. So, what can antibody drug conjugates do for us? Well, I think they’ve already shown us that we can improve outcomes for patients with metastatic disease and across a number of different subsets. So, HER2+, triple negative, and HR+ disease, have all have shown benefit from treatment with antibody drug conjugate with really remarkable improvements and manageable toxicity to a large degree.”

“Now, what we’d like to see is move those drugs even earlier to the first line setting. I mentioned, you know in talking about these drugs, I’ve always mentioned that chemotherapy a lot of it causes cumulative toxicity. You know, there are drugs you just can’t keep giving because patients have neuropathy, and neuropathy is so miserable for patients. You know, you can’t wear your shoes, can’t hold things as well.”

“Well, these drugs, the ones that are now available and have regulatory approval don’t cause neuropathy, you have to monitor for the side effects. But the cumulative toxicity is relatively modest. So, patients could potentially stay on for a long time, then we’re going to have to think about ways to maintain that response. Maybe give the drugs less frequently or something like that, think of maintenance. But if we can move this into earlier lines of chemotherapy, we still are going to use endocrine therapy and targeted agents.”

Dr Rugo’s Hope for the Future

“You know, maybe we could really improve that duration of time that patients have disease control, when their cancers are endocrine resistant or importantly for triple negative disease, where the majority of patients, more than 50% don’t qualify for immunotherapy. And then again, the overarching goal is to prevent recurrence of disease.”

“I think there’s two different approaches in early-stage setting. One is to take patients whose cancers don’t respond to the standard therapy and rescue them with these antibody drug conjugates. But then I think the next step is to maybe use the antibody drug conjugates up front, so that we can potentially have even better responses with maybe less intensive therapy that doesn’t have the some of the risks that chemotherapy does.”

“So that’s the biggest picture, looking at the farthest ahead of where we may be in the next few years, as we continue to test these novel agents. And of course, there are new antibody drug conjugates being produced and tested, and so there’s a lot of room for even greater improvements and newer targets and newer toxins.

Breast Cancer Prevention

Women who have a 30% chance of developing breast cancer over their lifetime are classified as very high-risk individuals. While preventative treatments, including a bilateral mastectomy, certain medications and regular breast screening can be effective in reducing the risk of breast cancer, these aren’t always an option for some patients.

While there is no way to prevent breast cancer, there are steps that can be taken to lower one’s risk of being diagnosed, particularly for women with a strong family history or those who carry a gene mutation.

The theme for Breast Cancer Trials 43rd Annual Scientific Meeting (ASM) was Breast Cancer in Young Women.

We asked Dr Wanda Cui what the differences are in prevention, screening and diagnosis of a young women compared to postmenopausal women.

“I guess we know that in Australia, the screening program or the national screening program really focuses on older women because we know that the risk of breast cancer tends to increase with age.”

“However, we know that, certainly over recent decades the risk of breast cancer in younger women is also increasing as well and certainly that incidence is rising. In terms of the difference for screening and prevention for younger women, at the moment for women under the age of 40, we don’t routinely offer screening and certainly some of our traditional screening methods, like mammogram, can have a lower sensitivity in these women as well.”

“Also, for young women, there’s a group who are at higher risk because of genetic factors, which may increase their risk of developing breast cancer at a younger age, and one of the troubles is that it’s not common. One of the troubles is trying to identify who those women are, who has an increased risk and should be offered earlier screening as well as prevention strategies to try and reduce their risk of breast cancer both at a younger age, but also into older age as well.”

“I think that’s a real challenge in terms of prevention in young women and that kind of education piece of: What is my risk? How do I assess it? How do I know what screening should I have? What are the strategies to try and reduce my risk of breast cancer, if I’m found to be at an increased risk?”

Where is Research Currently at in Preventing Breast Cancer?

“So that’s a good question, certainly for women who are found to be at a high-risk of breast cancer, which is if you’ve got a chance of developing breast cancer of 30% or over throughout your whole lifetime you’re classified as very high risk.”

“For those women in general we would discuss things like a bilateral mastectomy, which is where you have your breasts surgically removed, which we know is very effective at reducing the risk of breast cancer in those very high-risk women.”

“But that’s not necessarily for everybody and in women who are at increased risk we would also recommend regular screening, but also there are some medications that can be used to try and reduce your risk. Things like tamoxifen as well as anastrozole have been shown to reduce your risk of breast cancer by anything between 30% to 50%  and not only when you’re on the tablets, but also for the years following as well.”

“The trouble with those tablets is they only reduce one type of breast cancer, which is HR+ breast cancers and not so much for HR- breast cancers. That’s something that we need to do more research into, how do we prevent those cancers in women who choose not to have bilateral mastectomy surgery to have their breasts removed?”

“That’s one area that BRCA-P is really addressing. In those BRCA-1 carriers, we know that HR- cancers tend to be the more prominent type of cancer that these women develop. And whether or not this drug could reduce that, I think that would be practice changing if we found out that was a positive study.”

What are Modifiable Risk Factors for Young Women?

“So, increased exercise, even in somebody who’s not overweight is still important for reducing your breast cancer risk, as well as reducing levels of alcohol. We know that there’s no safe threshold below which you are safe from developing breast cancer. But we know that the more alcohol you drink, the more it increases your breast cancer risk. So really trying to minimise that, not only from a breast cancer perspective, but also from a general health perspective as well.”

“One challenge is that we know for very good societal reasons, especially as women become more educated and are moving into their careers, that childbearing is now delayed and breastfeeding may not be for as long as we what it used to be. And we know that those are some risk factors for breast cancer, but I think we have to weigh that up with the risk of breast cancer, which is only slightly increased, versus the very beneficial reasons for why women delay childbearing.”

“I think there’s no there’s hard rule here, and I think we must weigh that up for each individual woman. Certainly, in countries like Sweden and there have also been some studies conducted in the US, where they’ve shown that encouraging women to have parental leave has been a way to improve longer breastfeeding.”

“That might be something that we can look at from a policy standpoint, which would benefit women from a breast cancer perspective, but also just in general from a societal perspective as well.”

Dr Cui’s Hope for the Future

“If you don’t shoot for the stars, you don’t ever get there. So, I think breast cancer prevention is important. It may not be as sexy as some of the new treatments that come out of breast cancer treatment, but we know that even if we do cure a woman of breast cancer, going through that journey is hard.”

“If we can try and prevent more women from being diagnosed in the first place, I think that that’s a great goal to aim for.”

Health Economics in Clinical Trials

Health economics is used in clinical trials to ensure information is being collected in the right way, so that it can be provided to Governments and bodies such as the Pharmaceutical Benefits Advisory Committee, so that they can compare new treatments with existing treatments to decide what drugs should be funded in the public system.

“So, health economics looks at how we use health care resources and how we can use them to better provide access to health care. And we use it in clinical trials to be able to go to someone like the minister or the committees that support the minister, like the Medical Services Advisory Committee, or the Pharmaceutical Benefits Advisory Committee so that they can compare new treatments with existing treatments to be able to say yes, this should be funded in the public system.”

“It’s critical to be able to make those comparisons about what we’re doing now with what we want to be doing, and health economics helps us to do that – to compare the costs and the outcomes in the right way to make decisions about value for money.”

Does the Role of Health Economics Differ Depending on the Phase of the Clinical Trial?

“It certainly does, and we always try to say that there is a role for health economics in the different phase trials. It’s just that that role, as you say, is quite different. So, for example, in a phase one trial, we wouldn’t be looking to make any comparisons because there isn’t a comparison in a phase one trial, but we still might be interested in understanding what it takes to implement whatever is being tested in the phase one trial.”

“So, if it’s a new drug that we’ve never seen before, we might want to know what are the resources that are required for patients to use this drug? Is it expensive? And that’s important for us to understand for the next phase trial for the next phases of that drug if it passes phase one.”

“If you compare that to a phase three trial where we’re comparing something that we know is effective with the current standard of care, then doing a health economics study as part of that trial is important because if that study is positive, then we’re going to use those results or someone’s going to use those results to go to a reimbursement committee and say this should be funded.”

“So, it’s critical that we’ve got good information about the costs and the outcomes for the new intervention compared with the standard of care, to be able to demonstrate that value for money.”

Does an Economic Evaluation need to be included in Clinical Trials?

“Not in every trial. We don’t need to do economic evaluations in every trial. It really depends on what we’re aiming to do with the trial. So, if the trial is aiming to change practice, then ultimately we want to affect practice change either at the local level or the national level.

“Having an economic evaluation alongside that trial or as part of that trial is something we would want to do because having an economic evaluation is a good way to change practice. We’re able to say yes, this thing represents value for money, particularly if it’s changing practice at the national level where we want to make treatments available in a publicly funded way.”

“If the aim of the study is not to change practice, but to show that something works so that we can go on to our next phase of our study, then doing an economic evaluation might not be required. But we still might want to collect some information about how that drug is working, either in terms of its costs or in terms of its impact on patients.”

“We have to remember that health economics is a two-sided coin. It’s not just about what it takes to deliver an intervention, it’s also about the impact of that intervention. So we might want to collect information, for example, about quality of life or the impact on patients in terms of time requirements. So, you know, how long the patients are having to go to the hospital or to the clinic, and how long are they there for while they’re receiving treatment, so that we can understand what the impact is on a patient from a time requirement, which in itself has implications for treatment and its value.”

Associate Professor De Abreu Lourenco discusses the importance of assessing efficacy in health economics.

“So we need to be able to assess efficacy in a way that’s comparable, and quality of life allows us to do that because we can look at not just how well people are living, so not just looking at survival, but looking at the combination between survival and quality of life.

“We do that using a variety of questionnaires that we ask that patients are asked to complete and then we value those patient ratings of their health by members of society.”

“So a patient tells us what it’s like to live with a certain condition and then society has told us what they think about that condition and how they would value being in that condition themselves. That societal evaluation often sounds a bit perplexing to people. They think, well why should we care about how society values a particular state of being in terms of quality of life? And the reason that’s important is because usually the information that comes out of those questionnaires is being used to make decisions about how we spend societal dollars and that’s why we get societal values of those of those health states.”

“So how does society decide what is important? Such as making a new drug available to everyone the way that we do that in the countries where it happens. So, countries like Australia, New Zealand, Taiwan, the United Kingdom, and Canada. There’s a number of countries where this happens, and there is typically a committee that’s made up of members of society who meets to assess a package of evidence that’s submitted by whoever the sponsor or organization is for the intervention.”

“In most cases that’s the company who makes or supplies whatever that intervention is, whether it’s a new drug, or a new diagnostic device, or a new imaging device. They will ask this committee to put it on the publicly funded list. The committees look at the evidence in a number of ways.”

“They’re looking to see, well is it safe? You know, if we fund this thing, is our public going to be safe? Is it effective? Does it do what it purports to do? At least as well as what we’re doing now and hopefully better? Is it cost effective? What that means is does it represent value for money.

“So, if we spend our money on this new intervention, would we be buying more outcomes than we get with the way we’re doing things currently, and are we prepared to pay as much money as the company is asking for them? So, is the money that the company is asking for those extra outcomes, worthwhile? Are we prepared to pay that much for those additional outcomes?”

“All of that evidence gets submitted to these committees and they have to think about it? They must think about it in a number of ways. So is it safety effective and cost effective. But they also think about it in terms of if we don’t fund this thing, are there equity implications? So, will patients be worse off if we have to make them fund it themselves? Are their equity implications? If we do fund it, will some patients be worse off than others?”

“For example, Australia is a great example where rural patients can sometimes be made worse off if we find something that’s only going to be available in the city. So how does the rural patient get access to something that’s only going to be available in the major metropolitan cities? What happens if we’ve got a condition that’s for very, very few people? How do we make sure that they’re going to get treatment, because those treatments can usually be very expensive, but we don’t want to deny them access just because it is expensive.”

“That means it’s going to be prohibitive for any company to provide it at a cheaper price. There are lots of other things that they think about and not just that cost effectiveness element. So, it’s a very big decision that these committees have to make, and they do it quite advisedly. It takes a lot of thinking and they put a lot of effort into it.”

How is Health Economics Data Collected?

“The gold standard way to do it as part of the trial. So, you know, ideally when a trial is kicking off, we want to be there day one when the protocols being written. We want to know what the study question is, can we incorporate health economic data endpoints or data capture throughout that protocol?”

“So, when we get to the end of the trial, we have the data, and the information that we need to be able to go away and do the economic evaluation. That’s the gold standard. That’s the best way. So that you know, we have everything that we need to be able to answer the questions in the right way and as robustly as possible. That doesn’t mean we can’t do an economic evaluation if the trial has been conducted and suddenly, we decide or someone decides this really needs an economic evaluation, it can always be done. It’s just it becomes more challenging to what we call retrofit and economic evaluation if the information has already been collected for the efficacy component of the trial but can still be done.”

“But yes, the gold standard is to do it when the trial is happening, when a clinical trial has published results and it may be very positive for a new treatment.”

Is there a Heart in Health Economics or is it all Numbers?

“So, there is research that’s ongoing at the moment that’s looking at what is included in quality of life, to expand that. So, we are capturing things that at the moment might be considered far more intangible than many aspects of quality of life. So there is research looking at things like hope, for example, and saying well can we expand how we think about quality of life to capture something like hope, and that’s certainly bringing in more and more of that element of hope.”

“And I’ll share an anecdote with you. Many, many years ago I was coming back from a trip on a plane and I was sitting, working away and the whole flight, an older couple next to me kept looking at what I was doing. And at the end of the flight the gentleman worked up the courage to finally ask me some questions and he said excuse me, but did you work on that drug? And I said yes, why? And he said our son had leukaemia and he went on that drug and it saved his life. I just want to thank you for making that available in this country because without it he would have died.”

“At which point his wife started crying, he started crying, and I started crying and it brought home to me that I do what I do because it does impact on people. And you know, the nature of health economics is particularly about impacting on people’s lives and that’s all about heart. So yes, it’s underpinned by head the numbers but it’s all about heart in its application.”

Evaluating the Clinical Performance of NASHA Gel Compared to Surgical Clips

Radiation therapy after breast conserving surgery plays an important role in the management of early breast cancer, decreasing the risk of breast cancer returning and improving mortality rates.

As part of a Clinical Fellowship project with Breast Cancer Trials, Dr Janice Yeh is evaluating the technical feasibility and clinical performance of the novel NASHA Gel compared to standard surgical clips as a fiducial marker. We asked Dr Yeh to explain the role that radiation therapy has in the treatment of early breast cancer.

“So, radiotherapy targeting the breast tissue after a lumpectomy surgery for early breast cancer improves long term survival outcomes and local control. It’s basically the equivalent to having a mastectomy, which is having the breast completely surgically removed.”

“It allows women to preserve their breast tissue without compromising on oncological outcomes.”

What is a Fiducial Marker, and How are Surgical Clips Presently Used?

“Fiducial markers in general are usually small metallic objects that are placed near, or at the site where we want to treat, and it helps us be more accurate with targeting the treatment.”

“Surgical clips have been around for many years. They do stay in the body usually permanently, however you shouldn’t be able to feel it. The potential downside to them is that we are limited in the number of clips we can put in because, they can potentially cause metallic interference when it comes to scans that patients might have in the future.”

What is NASHA Gel?

NASHA gel is a type of hyaluronic acid, which is a common ingredient in serums and creams, and it’s a naturally occurring substance in the body. Dr Yeh explains why NASHA gel might be better than surgical clips as a fiducial marker.

“NASHA stands for ‘Non-Animal Stabilized Hyaluronic Acid’, which just means it’s a manufactured form of hyaluronic acid where it’s, stabilized in a manner that improves shelf life and longer half-life for clinical use.”

“Because of the gel like consistency of it, the surgeon is able to inject little dots of it as points of reference for the fiducial marking of the tumour bed to help with being more accurate with radiotherapy planning.”

“It’s designed to be biodegradable over time, and so we can put as many dots in as needed, we’re not restricted in the same way that we might be with clips.”

“So as an example, a common number of clips useful for fiducial marking is probably around four, whereas with our study there can be as many as 16 dots put in when using the gel. If you think about it, having more points should allow us to be more accurate and be more consistent with knowing where we’re treating, and therefore targeting the most at risk area of the breast after breast cancer surgery.”

An Overview of Dr Yeh’s Project

Developing new research ideas and supporting the next generation of researchers is at the heart of the new Clinical Fellowship Program.

The Program is aimed at early career researchers, who have a high-level interest in clinical research and qualifications in the disciplines of medical oncology, pathology, psychology and other supportive care specialties, radiation oncology, radiology or surgery.

“So, my research with Breast Cancer Trials is a pilot feasibility study, where we are wanting to compare the consistency of being able to draw out the tumour bed using the clips versus the gel.”

“At the time of surgery after the lump is removed, the surgeon puts in both the gel and the clips into the same patient. Then when it comes time to planning the radiotherapy, we have the patient undergo a CT scan as well as an MRI scan. We then use those images visualize the fiducial markers and compare the consistency with delineating the tumour bed.”

“So, we have a team of six observers, five radiation oncologists and one radiologist, and once the patient’s scans are done, they sit down and draw out what they think the tumour bed is. We then compare against each other to see which using which fiducial results in the least inter-observer variation.”

“We started recruitment for this project last year, and as of late May 2022, we’ve recruited more than three quarters of our target number of patients.”

Dr Yeh’s Hope for the Future

“I mean obviously I’d like to be able to have firmer results before we can be clearer about our next step. The company that I’m working with to produce the NASHA gel, are in development of a radio opaque version of the gel. So once that comes along, I think it would be important to also validate our results with this newer form of the gel and then make it make it more accessible.”

“We are also looking to increase follow up in terms of formally reviewing the patient’s annual post op mammograms with a specialist breast radiologist, to see if the gel is still visible. The degradation varies quite a lot depending on the amount that was injected, where it was injected, and the patient’s natural biology. So, we think it’s really important to assess this more formally.”

To find out more about Breast Cancer Trials Clinical Fellowship Program, follow the link below.