Lotjpa Yapaneyepuk (Talk Together): Bridging Communities and Cancer Research

 Access to clinical trials isn’t equal. and for Aboriginal and Torres Strait Islander peoples in Regional Victoria, barriers in accessing treatment for breast cancer remain Dr Monica Green and Ms Leah Lindrea-Morrison share an initiative that’s breaking down those barriers by talking together, listening deeply, and creating culturally safe pathways to clinical trials/

“I’m Monica Green, I’m currently the Coordinating Principal Investigator with the Border Medical Oncology Research Unit on a project called, Lotjpa Yapaneyepuk, which means ‘talk together’ in Yorta Yorta language about cancer trials.”

“My name is Leah Lindrea-Morrison, and I’m a Yorta Yorta woman from Shepparton in Victoria. I’m the research assistant for the, Lotjpa Yapaneyepuk Talk Together About Cancer Trials project. So, my role is to lead the community engagement part of the project, including leading the Aboriginal and Advisory groups and also the yarning sessions. And I’m also advised on all aspects of the project.”

“The yarning sessions is a way to find out what community knows about cancer trials and working with them to co design a resource. The information stories shared at the yarning sessions will guide the content and format of the resources that will be developed.”

“I’ve had my own lived experience with breast cancer, and I’ve had a husband who passed with cancer. But also having a young family while my late husband was diagnosed and also having my own diagnosis, I’ve seen first-hand the impact that it has that can have on families”, Leah said.

“Cancer is the leading cause of mortality in Aboriginal and Torres Strait Islander people now, which has only happened in recent years. It’s a major issue, and survival rates are not improving. So, there’s an area of huge need there. And this is evident through the yarning sessions that Leah has been doing as part of the Lotjpa Yapaneyepuk project”, Monica said.

“People are so engaged in it because everyone’s affected by it. There are also low trial participation rates for Aboriginal and Torres Strait Islander people, which is difficult to quantify because it’s not thought that people identify all the time and so it’s difficult to get accurate figures.”

“So, it’s really good to focus on this area of need. And just seeing how engaged the community is, and that includes our community members, but also the staff members of the Aboriginal Community Controlled Health Organisation that we are working with, Rumbalara Aboriginal Cooperative, in Shepparton, and their staff are part of our steering committee and our Aboriginal Advisory Group, which just signifies what a priority it is for the community.”

“Just briefly, I think some of the barriers are the mistrust or fear of research. Obviously in the past, research was done about aboriginal people and so some of those fears are still there. And also, trial design, so the type of cancer being researched, and often there isn’t enough research into the cancers that are common in Aboriginal and Torres Strait Islander people. Strict inclusion criteria and location are other issues. Many clinical trials are coordinated in metropolitan areas, not so much regional,” said Leah.

“I do understand that they are trying to make that happen, but currently taking some Aboriginal people from their community and family has large impacts and can be a huge barrier for people. So, there’s no consideration of cultural aspects of life in the trial designs, implicit or explicit bias. Taking part in a trial may not even be discussed with the person. But also, the language and communication of trial information is something that needs to be addressed.”

“So generally, the information is in a medical (Western) way of talking. So, there’s few Aboriginal and Torres Strait Islander people that, are in the research teams and also that there’s insufficient support for patients there. As well as this the demands or cost or taking part in trials are too much.”

How do historical, cultural and systemic factors influence trust in medical research and clinical trials among indigenous communities?

“Leah’s talked about the history of medical research and there’s been damaging and disrespectful practices, which you might think are in the past, but actually, it still goes on and it’s really damaging to the trust of Aboriginal people, especially to not get any results from research that they’ve been involved in, and to not hear anything about it,” Monica said.

“Even if the medical team has taken their blood or interviewed them, nothing comes back and that makes you very disinclined to take part in the next research project that comes along. And I think with clinical trials in particular, people might feel like they’re a Guinea Pig, they don’t want to be randomised, there’s a lot of issues around that which need to be discussed in yarning sessions or when people are chatting to their oncologists.”

“From the cultural perspective I’m a non-Aboriginal person and have been working in Aboriginal and Torres Strait Islander health research for 10 years or so, and it’s become very apparent from the people I’m working with and the people that we’ve been researching with. That trust is a huge issue, and also that healthcare for many Aboriginal and Torres Strait Islander people is culturally bound and you can’t ask people to separate their medical condition with their cultural obligations. And health professionals need to be receptive to that and understand and respect it rather than try to change it.”

“From the systemic factors we are working in a largely western medical system, which is often very unfriendly and very culturally unsafe for people even when having the Aboriginal and Torres Strait Islander flags around, or having aboriginal liaison officer available to support people when they come for cancer diagnoses or treatment or participation in a trial. It’s a really important aspect of people engaging with their treatment.”

Can you share any strategies or initiatives that have been effective in improving access or building those stronger relationships with communities in regional Victoria?

“I think it has to be something that the community will benefit from, I think that’s really important. It’s he starting point because it’s no use saying let’s do this, and it’s not something that the community want or need. I think that’s the success of any project, having local knowledge and experience, and having people from that area being part of any research, and having those relationships with your community,” said Leah.

“I just mentioned then with the local mainstream cancer services, it’s important that our community has a voice and that they feel that they’re being heard, to make things more successful. Also, the community based participatory research and co-design, for example, in co-design one of the principles is inclusive partnerships. This means fostering and maintaining equitable and collaborative relationships between all participants. Establishing appropriate communication channels and conflict resolution processes formulated by and with community that retains trust and support authentic partnerships using imperative.”

“And that’s where Monica was talking about trust. If there’s no trust there, then good luck. And lastly, I would say advocacy to make sure Aboriginal and Torres Strait Islander people have access to pharmaceutical trials.”

What role does community engagement and co-design play in creating a more inclusive and culturally safe research opportunity for patients?

“You’ve got a much better chance of reaching your audience if they’ve been involved in creating the content and making it meaningful and relevant. And so that experience when you’re doing co-design of going out to community and hearing from the people who will be recipients of whatever you produce is so valuable,” said Monica.

“It’s not just for the act of receiving that information, but it also creates positive relationships, which is hopefully the aim. It creates awareness of the issue already and people start talking about it. As I said before, everyone’s affected by cancer in some way. Basically, whatever you’re developing will be much stronger and have a greater likelihood of doing what you want it to do.”

“And in, in our case for Lotjpa Yapaneyepuk, we want to create resources about clinical trials that reach Aboriginal and Torres Strait Islander people so that they’re aware of clinical trials and myths are dispelled, such as you’re not going to be a Guinea Pig sort of thing.”

“So that if, and when, people are diagnosed with cancer or they have a family member who’s diagnosed with cancer, they are already equipped with some knowledge about clinical trials. And we want to end up with some videos that people can just watch for two or three minutes to learn what a clinical trial is, in a way that’s understandable.”

How can clinicians and researchers better support Aboriginal and Torres Strait Islander patients to consider and navigate trial participation?

“First of all, recognising that the relationship between clinicians and Aboriginal and Torres Strait Islander people is a critical aspect of that engagement with treatment. And so, with cancer treatment, it’s often not possible to have developed a strong relationship before treatment or being offered a clinical trial. But the way in which the decision is held is likely to have a significant impact on how the trial information is received,” Leah said.

“For example, does the person feel respected? Are their questions being answered? Are their responses being respected? But also, I think that you get all this information just knowing that you might have somebody else that you can recontact.”

“And I think it’s that first initial contact if you feel comfortable, that relationship has already started to form. So other strategies include the Aboriginal workforce development, patient navigators or care coordinators as part of the team, telehealth trials, cultural safety and equitable care that help to build trust.”

“Using language that they will understand, no medical jargon. Becoming familiar with the key principles and guidelines for research and practice. So ethical guidelines through the NHMRC code of ethics. And obviously the people that are researchers will understand these acronyms. Another one is utilising a quality appraisal tool. And for health services it’s about following the National Standard, the user-guide of cultural respect from the Department of Health.”

What does a more equitable and accessible clinical trials landscape look like and what needs to happen for us to get there?

“The big picture aims to improve cancer outcomes, and one way of doing that is by increasing participation in cancer clinical trials. And to get there, it’s multifaceted and needs to be approached from every level of the health system. And that’s from pharmaceutical companies. Developing trial designs that are not so restrictive”, said Monica.

“Not having such strict inclusion and exclusion criteria. Looking at ways that the trial managers can support Aboriginal and Torres Strait Islander people to help with their participation. What time of day is best for you for appointment, and why? If you can’t come because you’ve got, you are looking after your grandchild or you’re looking after your parents or something, then can we pay for someone to do that?”

“We need to start looking at other solutions to recognise why people might say, I’m not going to participate because I’ve got other priorities. So, there’s that level at the health system and cancer health professionals, and that’s part of what Lotjpa Yapaneyepuk is doing, by trying to raise awareness of the strategies that might connect Aboriginal and Torres Strait Islander people to the clinical trials.”

“There are other people working in this area as well. Lots of people are approaching it, and our project obviously is focussed on a community level where we’re talking to community members and developing resources as advised by them and our trial experts. But while we are working at community level, we hope what we will develop will be used at a national level and will continue to reach Aboriginal and Torres Strait Islander people outside country.”

“And obviously it doesn’t stop there, there’s a whole range of different avenues to increase awareness and different sorts of resources that could be developed. But I think the key thing is that discussion needs to take place in a culturally safe way. You can develop all the resources you like, but if the offer to take part in a clinical trial isn’t made, or is made in such a way that you alienate the person who you are treating, then that’s not what we want, that’s not a good outcome”, Monica said.

4CASTING the Future: Innovations in Triple Negative Breast Cancer 

 Triple negative breast cancer remains one of the most challenging types to treat because it lacks the common treatment targets, grows and spreads aggressively, is highly diverse and currently has limited effective therapies – but new research is changing the story. 

Associate Professor Rachel Dear takes us inside the 4CAST trial showing how science moves from bench to bedside and what this could mean for the future of triple negative breast cancer treatment. 

“The forecast study is looking at a new treatment for metastatic triple negative breast cancer, in particular, androgen receptor positive metastatic triple negative breast cancer. The study drug is called INO-464, which is an androgen receptor antagonist.” 

“This treatment drug also blocks the production of androgens as well, and in preclinical models, so that means in the laboratory it slows down the growth of cancer and delays time until new metastases occur in preclinical models of metastatic triple negative breast cancer.” 

“And it does this in in combination with IV treatment, including different chemotherapy agents. And so now because of these promising laboratory results, we are testing this in people.” 

Triple negative breast cancer is often described as one of the more challenging subtypes to treat. What makes it so difficult and how does this research aim to change that?  

“Triple negative breast cancer is a difficult type of breast cancer to treat, and in fact, it has the worst prognosis out of all the different types of breast cancer with a median overall survival of only about 18 months.” 

“This is because historically there hasn’t been a target to focus on. It’s defined by its lack of target: estrogen, progesterone, and HER2 are all negative. Unlike hormone receptor positive breast cancer or HER2-positive breast cancer, where we actually have a defined target.” 

“So that’s why it’s difficult to treat, and that’s why this study is so exciting because we’ve identified the androgen receptor as a target for triple negative breast cancer.” 

The phrase ‘from bench to bedside’ suggests this research has come a long way. Can you walk us through how the preclinical findings led to this clinical trial?  

“So, the preclinical findings are the work of Christine Schafer’s lab at the Garvin Institute, where she has been working on repurposing drugs and looking at new indications. In particular, SNOL, an androgen receptor antagonist that has been looked at in prostate cancer.” 

“And then there were early trials internationally looking at its role in breast cancer. But then she started testing it more in the lab, in metastatic triple negative breast cancer cell lines, and found that when she combined it with chemotherapy, rather than giving it by itself, it had much better results because in earlier trials in humans, it had just been given by itself as a tablet.” 

“But when she combined it in these mouse models in the lab combined with chemotherapy, she found that it resensitized the cancer to chemotherapy which meant the cells died better and were controlled for longer.” 

“And so, she’s worked out the exact mechanisms of why this occurs. It changes cell state, it makes cells more sensitive again, when previously they were resistant to chemotherapy, so unless Christine’s lab had done this work, we wouldn’t have then progressed to testing it in a clinical trial in human beings.” 

“I first met Christine almost six years ago. She came to me with this exciting work, and she showed me the graph, and said ‘look what’s happening to these cell lines, what do you think about this? Do you think that this would work in human beings? We know that as a single agent, as a tablet, it’s really safe. Do you think we combine it with chemotherapy?’ So then that meeting between Christine and myself then led to the idea of actually testing whether the combination of the tablet and chemotherapy in human beings are safe, and also now looking to see if it’s an effective combination as well.” 

“It is a phase one a trial, and the purpose of a trial like that is initially to check that the combination of chemotherapy and SNOL is safe. And we have completed that part of the study, which is called dose exploration. So, we are trying to work out what is a safe dose of SNOL to combine with chemotherapy.” 

“We enrolled eight patients into that study, and six of them were eligible for the safety component of the study, and we found that the dose that we started with of SNOL was safe combined with chemotherapy. And we know that this is the same dose that as a single agent was also safe and effective. And it was good to know that unlike other phase one trials.” 

“We were already giving an effective tablet at it. You know, that was likely to be efficacious, and it was such a relief that it was also safe and well tolerated as well. So now that we found in those six patients, the combination of TER and chemotherapy was safe, now we’re into the part of the study called dose expansion, where we are combining the treatments.” 

“And the goal of this part of the study is to see if the combination is effective. The good news was that we already got some early signals of efficacy of chemotherapy combined with SNOL. And in fact, out of those six valuable patients, five of the patients had stable disease. And in a couple of patients, that was quite a prolonged, duration of response to the combination treatment.” 

“So, a hint that what Christine was seeing in the lab, we were also now seeing in our patients in the clinic. The main side effect issue has been not related to the SNOL, but related to chemotherapy. We’re using taxane chemotherapy, either docetaxel or paclitaxel, and a lot of patients have already received that type of chemotherapy.” 

“This means they’re vulnerable to a side effect called peripheral neuropathy, which can cause numbness and tingling of the fingers and toes. And so that’s quite a common reason people come off the study due to that side effect, not because their cancer started to grow.” 

And so how close do you think we are to seeing this move beyond the trial setting? 

“We currently have three people enrolled in dose expansion, and we need between 25 and 29 patients. So, we really need to increase our recruitment to the study. It’s going well, but we need to increase it. But an exciting development is that we just got ethics approval for a decentralized trial model, which means that the chemotherapy can be given as standard of care in a patient’s local hospital by the usual oncologist, and we can ship tablets from the King Hall Cancer Center to the patient.” 

“Using telehealth appointments, we can monitor what’s happening with that patient on trial. So, it takes away issues such as governance at another site. It takes away the time and travel, you know, from a patient who might live in a regional area in New South Wales.” 

“They don’t have to fly to the Kinghorn for this treatment. They can have it all with their usual oncologists. So, I think that by giving that opportunity to enroll in the study that way, that will increase recruitment. And using that telehealth trials appointment, we can already kickstart pre-screening for the study because we have to check their androgen-receptor positive.” 

“That can be done locally and often it is now being added to a triple negative breast cancer pathology report. But we can also get that tissue and test it at St. Vincent’s Hospital as well. And that can all be started early on.” 

What excites you the most about the potential of this research and what it could mean for the future of treating triple negative breast cancer? 

“I’m excited that this treatment offers a targeted treatment approach because I think many patients feel quite disheartened that the main treatment option that they’re offered is chemotherapy. They often think, surely there must be a new treatment that works better than just chemotherapy. So, I think that offering them a targeted therapy that’s well tolerated, that’s a tablet, is very exciting.” 

“And there are other targeted treatments now being studied for triple negative breast cancer. For example, antibody drug conjugates, immunotherapy. But I think that the Tylenol tablets even combined with these new treatments may make them work better. Not just making chemotherapy work better, but even some of these newer treatments.” 

“So perhaps that would just be for AR-positive metastatic triple negative breast cancer, you could still have your immunotherapy. But take an antibody drug conjugate, take your SNOL tablet and maybe it will sensitize the cancer cells to work to be even more responsive to some of the other new treatments coming along.” 

Breast cancer treatments save lives, but sometimes it can leave the heart at risk. Professor Thomas Marwick sheds light on cardiac care for breast cancer survivors, exploring how monitoring and management strategies can protect heart health long after treatment ends.

“I think it’s a very important consideration, and I think we’re recognising increasingly that this is the case. The data is that for women with cured breast cancer their chance of dying from an illness is much more likely with a cardiac illness than their original cancer. And there’s several reasons for this. It seems as though heart failure is the dominant issue here rather than, for example, coronary disease.”

“And there’s several drivers for it. There are probably similar things causing the cancer that cause the heart failure. The toxicity of some treatments is important and then there may be some direct effect of cancer on the cardiovascular system that increases the risk as well.”

What are some common cardiac risks or complications associated with breast cancer therapies?

“The way I look at this is really at the time of treatment and then afterwards. So, at the time of treatment anthracyclines are a group of cancer-treating chemotherapy that have been used for a long time and are decreasingly used in breast cancer, fortunately, but still required in some situations.”

“And then there’s a number of other molecules such as trastuzumab, that are used for this as well. Both of them can have adverse effects on cardiac function. So, we monitor the heart very carefully during cancer treatment and it may be necessary to initiate some sort of protection. And then after cancer treatment people have got some legacy of their cancer or their treatment that goes on for years.”

“And then on top of that, various things happen in people’s lives. They gain weight, they get diabetes, they get high blood pressure. All of those things are drivers of heart failure, and so we think that it’s important to have some sort of ongoing surveillance for cardiac problems in addition to the normal cardiac prevention strategies of controlling blood pressure and cholesterol and those kinds of things.”

Are patients typically monitored during and post-treatment?

“It depends on the nature of therapy. If either of those treatments that I mentioned anthracyclines or trastuzumab are being used, then usually an assessment of cardiac function, most commonly an echocardiogram, an ultrasound test to the heart, is done at baseline and then with some frequency during follow up.”

“Different oncologists and different cardiology groups use slightly different strategies for this, but essentially the cardiac function should be checked in that year of cancer treatment. We would say four times. Obviously, it depends on the circumstance and the level of risk, and then afterwards, I think there’s a need for the patient or the person who’s being cured from breast cancer to be followed up by their GP in the knowledge of what they’ve been treated with, because that will impact on the threshold of monitoring.”

“But certainly, awareness on the part of the patients is really important here, so that people who, for example, are developing exercise intolerance with the passage of years, that often the response is I’m just getting older, or I’ve put on a bit of weight, so I’m getting a bit short of breath.”

“You can’t afford to make that sort of decision in the context of having treated breast cancer. So, awareness on the part of the patient and the doctor. There is a lot of controversy at the moment about whether people should have ongoing monitoring with echocardiography. I think it really depends on the risk, and we have worked on a risk score to try and understand this a bit more, but it’s work that needs to be tailored to the patient.”

Are there challenges in balancing effective cancer treatment whilst needing to protect cardiac function for certain patients?

“I think that is often a concern, but there’s protection that we would use to begin with are a group of drugs called neurohormonal protection. That’s to say ACE inhibitors, angiotensin receptor blockers and beta blockers. And they don’t really have an effect on cancer. There are some treatments, there’s one particular one called Dexrazoxane that has been used in people having anthracyclines.”

“The concern with that has always been that it’s detrimental to the effect of the anthracycline. I think the evidence is not pointing that way from my reading of it. But that is a concern. But in general, I think it’s reasonable to understand that these are separate things and the presence of the cancer shouldn’t inhibit the desire to protect the heart.”

“And of course, the thing that you most want to avoid is concern about the heart interfering with the cancer treatment itself. And that’s something that you know should occur very rarely indeed.”

Are there emerging technologies or approaches that could improve early detection or prevent cardiac issues from occurring in the first place?

“Yeah, we are really interested in that. One whole area that’s important here is exercise. Interestingly, I think this is most important in relation to the effect of chemotherapy on the heart. Because chemotherapy obviously involves lots of things, including blood vessels and muscles.”

“And we think that some of the problem here relates to reduction of activity and, therefore the reduction of the small vessels that the heart ejects into, which puts an increased load on the heart. And there is evidence that by exercise training during cancer, you’re able to avoid that process. So that’s important in terms of detection.”

“There are some new technologies that are coming through. Obviously, there’s a challenge of doing a repeated echocardiogram, and it may be possible to get similar information or at least screening information from an ECG not the sort of things that we measure on an electrocardiogram, but things that the computer can detect. And we are working very actively in that space. So, it’s not really for prime time, but it may be part of the future of surveillance in this situation.”

And are there things that patients can do to reduce the likelihood of cardiac events occurring during their breast cancer treatment?

“I think during treatment, maintaining activity is important and some centres, particularly overseas, are offering essentially a rehabilitation or a prehab process, if you like to try and stop people losing that functional capacity. I think attendance to controlling risk factors is really important. We track various measures of cardiac function, and I’ll never forget a particular patient I saw, while I was still working in America, who seemed to be doing fine and then came in and these measures were really seriously awry.”

“And I spoke to her about what was going on, and in fact, her youngest child had just left the family home to go to university, which of course, is a big deal. They travel right across the country, and her blood pressure was up, and it’s just an illustration about how standard risk factors impact cardiac function and on top of the injury of chemotherapy, that can be very detrimental. So, attending to the humdrum routine, and controlling one’s blood pressure is really important.”

And so, what advice would you give clinicians and patients about integrating cardiac care into survivorship planning?

“Look, I think that this is a very important area in multiple cancers. Breast cancer particularly but also haematological malignancies because they often occur in older people. I think the person at the centre of this is the primary care physician or general practitioner. They need to have knowledge of the nature of chemotherapy and the dose of chemotherapy. And although that sounds trivial, I can tell you as a researcher in this space for a number of years, I find that really hard to obtain.”

“And yet that is very influential in deciding how intensely to follow the patient up. So that’s important. And then if there are any areas of concern or any areas where risk factors are not being controlled, then seeking help early in the piece is very worthwhile.”

“So, there are a group of cardiologists now, an increasing group who are being trained in cardio-oncology, and this interface between cardiology and cancer. And that’s important and those folk bring expertise to this area. That will hopefully stop, the cancer patient of today, turning into the heart failure or cardiac patient of tomorrow.”

And so, what are your hopes for the future in this space?

“My hopes are very much related to the surveillance of this as a cardiologist, whenever I see a patient coming into the hospital with heart failure. I always feel this is an avoidable problem. This is a detectable problem early and people can get into really deep water and it’s avoidable. So, to me, the issue is about surveillance.”

“It’s about identifying people who are at risk and then maintaining some means of knowing when things are going awry and our work is very much focused on producing a kind of strategy of understanding clinical risk and then layering on top of it the artificial intelligence and ECG components, and then the echogram to identify people where the cardiac function is going off.”

“And then moving with cardiac protective medications to stop the situation getting worse and yes, I think we’re on the path to that, but it’s a lot to change and changing clinical practice is not easy. So there’s still work to be done.”

For many breast cancer survivors, finishing treatment isn’t the end of the journey – it’s the beginning of new fears. Fear of recurrence is one of the most common and distressing challenges patients face. In this episode, Associate Professor Ben Smith unpacks why these fears occur, how they affect daily life, and what strategies can help patients move forward with confidence.

“I am a Cancer Institute, New South Wales, Career Development Fellow, and a Senior Implementation Scientist at the Daffodil Center, which is a joint venture between Sydney University and Cancer Council, New South Wales. The focus of my work is on translating evidence into practice, particularly in the context of survivorship care.”

Fear of recurrence is something that many people who have been diagnosed with breast cancer experience, but it’s not always openly talked about. So how would you define it and how common is it among patients?

“It’s definitely the elephant in the room. It’s something that is incredibly common, as you say. We know about six out of 10 people living with and beyond cancer experience, moderate to severe fear of recurrence that’s associated with poorer mental health and quality of life and very common and intrusive thoughts or worries about the cancer coming back.”

“They can really make it difficult for some people in cases of severe fear of recurrence to really engage in their everyday activities but also plan for the future. But certainly, a lot of people feel quite isolated by these fears, hence why I think it’s really important that we advocate for health professionals to ask about fear of recurrence and screen people for those concerns.”

What are some of the factors that contribute to a person’s risk of experiencing high levels of recurrence?

“That’s one of the things that makes it tricky to identify a fear of recurrence in clinical practice. Despite what you might expect it’s not closely related to a person’s clinical characteristics. Things like the type of cancer they’re diagnosed with, or the type of treatment they’ve received, or the time since they’ve finished treatment. Something that we’ve found across all different types of cancer but breast cancer especially, is that it is related to age, so younger people tend to experience more fear of recurrence.”

“It’s also more common in women. And we do see it more common in people who have a greater number of side effects from their diagnosis and treatment, and those who have pre-existing anxiety or mental health issues. But yeah, it’s not an easy thing to say, well, a person with X, Y, Z characteristics has a fear of recurrence. Hence again, why do I think we need to be screening for this concern on a routine basis.”

How does this fear impact on a patient’s wellbeing, both emotionally and physically?

“So, there’s an interaction between a person’s physical experience or symptoms and their fear of recurrence. So physical symptoms are one of the most common triggers for fear of recurrence. People often interpret aches and pains that they have as a sign that their cancer might come back, and that’s, again, something where health professionals can advise on which symptoms might be more indicative of recurrence or less indicative, and also what patients should do in response to those symptoms.”

“In terms of the mental health impact, we know that it can have a big impact on a person’s level of general anxiety, and it also increases the likelihood of experiencing depression. In extreme cases it can cause a lot of social isolation or withdrawal, as people feel like they can’t talk to people about it or, or don’t feel like they can relate to people who might not have had cancer.”

“It can cause them to withdraw from those social relationships that they would otherwise, you know, get support and value from.”

Have you found that fear of recurrence is something that tends to improve over time for people, or is it normally that they have it and then that’s kind of it?

“Yeah, so that’s the unfortunate thing. Despite what you might expect, or the intuitive expectation that fear of recurrence might reduce over time, we see that that’s not the case. In many people who have higher levels of fear of recurrence, if it’s left unaddressed, that tends to persist sometimes for many years post-treatment.”

“So, it’s really important that we don’t assume that a person who might be five years post-treatment, doesn’t have these concerns because they’re very common, even in longer-term survivors.”

Are there support resources or interventions that have shown promise in helping patients manage this fear?

“There are quite a few different interventions available now for fear of recurrence. I guess where we have the most evidence is for individual interventions delivered by a psychologist in a one-on-one kind of context. And we know that this can help people with severe fear recurrence to reduce their concerns.”

“We’ve also now got a lot of brief clinician-delivered interventions like CIPHER that Jenny Lou developed, which are designed to be incorporated into routine care and in incorporate elements such as just normalising and validating these concerns, giving prognostic information, telling people what their risk of recurrence is and what signs to look out for.”

“And those have been shown to reduce fear of recurrence typically in people with mild to moderate kind of levels of fear of recurrence. We’re still lacking some options for the large group of about four out of 10 patients who have moderate fear of recurrence. There’s been quite a bit of work done looking at online interventions with varying degrees of success.”

“We have found that for some of those interventions, the levels of engagement, and subsequent benefit are not as good as we would’ve liked. But there’s been some work done recently looking at interventions that have just a little bit of clinician support embedded into them. And we’ve found that they have much greater engagement and efficacy as well. So, I think there’s a lot of potential there for those types of interventions.”

What would you say to someone who might be a couple years post-treatment who had just started noticing that these fears are becoming more prevalent?

“Don’t be afraid to tell people or express those concerns to other people. I think it’s something that we know is very common, not only in individuals affected, but also their caregivers or support people. And just by sharing those concerns, I think it can help lighten the load for both those parties to some degree.”

“Talk to your healthcare team about it because there are support options available that they can provide as well. There are also some great resources from places like the Cancer Council and the Australian Cancer Survivorship Center on fear of Recurrence, and they include tips around things like mindfulness, which can be helpful.”

“We know that a lot of the interventions are kind of focused on not trying to eliminate these thoughts. We know that they’re almost inevitable. We’re never going to be able to get rid of them, but we can help people to live better with those concerns and not let them dominate their lives.”

“So, getting some advice around things like relaxation training and meditation and mindfulness generally can be helpful. But if you do need further help, don’t be afraid to talk to your healthcare team about it because it’s a very common and understandable concern. And there is further support available.”

“The main message for clinicians would be to ask about it. This is a very normal and understandable concern for a lot of people. So, we need to normalise and validate these concerns and make people feel comfortable talking about them. And hopefully patients realise they’re not alone in these worries and that there is help available.”

“Even peer support can be a big help in addressing these concerns as well, just understanding that other people who are going through the same thing, and sharing those concerns with them.”

Is it time to rethink a ‘one size fits all’ approach to breast screening? Associate Professor Sanjay Warrier joins us to discuss the future of tailored breast screening, a personalised approach that could revolutionise how we detect breast cancer earlier and more effectively.

“I’m a breast surgeon in Sydney. I’m the  previous past president of Breast Surgeons of Australia and New Zealand, and for the last 10 to 11 years, been running our breast training program in Australia.”

“When we look at our screening program now, it’s a program that’s been present since the 1980s, and it considers a couple of factors including being female and getting older.”

“And we know when we look at risk, it’s ultimately not just driven by those two factors. So really the idea with tailored screening is to move it to a more unique and individualised approach, depending on your risk of developing breast cancer. And when we look at our program now, it’s from 40 years of age, every two years, but 50 to 74 is your age big group.”

“And again, that’s every two years for everybody. So, depending if you are at moderate risk based on family history and other things, or if you’ve got dense breasts, you’re still falling into a similar screening algorithm as everybody else.”

What are the main factors that might influence a more personalised screening strategy for someone?

“It comes down to the fact that we know there are high risk genes that really make a big difference. So, if you have a gene mutation such as BRCA one or two, and there are a number of moderate risk genes that also increase your risk of breast cancer, and that often comes out from prior history of breast cancer, or members having a history and then testing that those, that group tend to move into a really high risk and end up being on a different pathway to breast screen.”

“And then outside of that, we know that there are other things such as family history that may not put you at that really high risk but may put you at a moderate or a low risk based on family history, but above a normal risk with no family history.”

“So that’s one thing. But then we’ve got other factors as well. We’re looking at if you’ve had breast operations before, you may have had diseases that increase your risk slightly. And the benign disease that can increase your risk slightly is having an atypical ductal hyperplasia, which is a good example or a lobular carcinoma in situ.”

“They’re not technically cancer, but they do increase your risk. And then there are several other factors as well. We know lifestyle factors do play a role and the more we know that there’s an increase if you drink a lot, if you smoke a lot, if you’re obese, they all subtly increase your risk of breast cancer. And obviously over a lifetime there is an increased risk with hormonal exposures.”

What does the current evidence say about the benefits of tailored screening and is it possible for that to lead to early detection or fewer unnecessary procedures for patients?

“I think it comes down to the fact that if we were going to break up your risk based on being at low risk, moderate, and high risk, and not talk about the high risk group, you are ultimately going to capture more interval cancers in the high risk group by doing two yearly imaging and in that group, and potentially increase your rate of picking up cancers if you are also using other modalities for assessing.”

“With a dense breast, for instance, and someone who’s got a moderate to high-risk family history, there would be a potential advantage to having contrast imaging in that group. And I’d use the analogy of where’s Wally? So, when we look at those photos from when we were young and you’re trying to find Wally in there, it’s hard.”

“And that’s like the density in the breast. So, the idea of having a plain canvas to find Wally, that makes it a lot easier for the interventional group to detect the cancer.”

How are researchers and clinicians working to determine who might benefit from more or less intensive screening?

“So, there are a lot of researchers working in this space, and it’s not just in Australia. There’s been studies such as the WISDOM Study led by Laura Esserman in America, and we have a roadmap to personalised screening known as ROSA, which has involved the government here in Australia, and key stakeholders.”

“And ultimately the goal is to work out how to develop a platform to create the evidence and then implement varying aspects of that into practice. But there is a real drive, and I do feel there are groups that have the appetite to potentially reshape the way that we do screening.”

Looking to the future, how close are we to seeing tailored breast screening become part of routine care, and what would need to happen to make that a reality?

I think you need engagement from your stakeholders. It must be a priority. And it needs those stakeholders to then champion for change essentially. So, you’ll have the evidence, but then there’s the feasibility and pragmatism of distributing this firstly at certain sites and then being able to roll it out across a country, considering that breast screen is also about equity.”

“That’s another thing – are we going to be able to offer it in rural areas the same that we are in the Sydney, in the city? So it does need champions such as Professor Bruce Mann who is a good example, but there are others as well who have, who are passionate about it.”

“Ultimately, I do think it is key to continue coming back to why it’s important, because at the end of the day, we know as a breast surgeon seeing a breast cancer, that if we are able to find a cancer before it’s in the lymph nodes and before you know it’s large, we could potentially de-escalate the type of treatments we offer those patients, and make it a seamless sort of outcome for that patient.”

“So, really on the front end, I think if we can increase our diagnosis and be personalised about it, that would be fantastic. I really do hope that there is engagement with other groups. I know there’s been a lot with the government through the ROSA project. I think ultimately, it’s then taking those key stakeholders and trying to drive a narrative that increases the development of personalised screening. And the low picking fruit has been reporting on screening.”

“The fact that they’re now reporting on density of the breast means that it is a starting point towards working out how to then manage that group, so that’s the hope, and hopefully we are not in the same position in 10 years’ time.”

Young women with breast cancer often face unique challenges beyond their diagnosis, including long-term survivorship issues, fertility and family planning concerns, and a higher likelihood of aggressive cancers, but are there treatment pathways keeping up?

Dr Belinda Kiely explains the groundbreaking OPTIMA Young trial, part of the larger Path-for-Young Initiative that’s exploring how global collaboration could change the future of treatment for younger patients.

“The OPTIMA study, the main study has been running now for many years internationally, and it’s looking at whether a multi-gene assay called Prosigna can be used to help determine which women really need chemotherapy, and which women can be spared chemotherapy as treatment for their breast cancer.”

“And that study is open to people from the age of 40 and over. The study is trying to prove that the use of the Prosigna test is non-inferior to standard treatment where everybody gets chemotherapy and endocrine therapy, and that study is expected to produce results probably in the next year or two.”

“There will be some premenopausal women in that study, but it’s probably only going to be about a third of the population, so it will only be a subgroup. The study won’t really be able to answer with significant power the question of whether this test-based approach of doing the Prosigna is safe in premenopausal women.”

“What Path-for-Young is trying to do is answer that question, is it safe to use a test to select premenopausal women who can be spared chemotherapy? The premenopausal women who have been recruited to the OPTIMA study over the last several years will be included along with an extension of the OPTIMA study, looking specifically at premenopausal women aged 18 to 55.”

“And then in Europe there’s going to be a separate OPTIMA-Young Study with similar eligibility criteria and a similar design where again, premenopausal women will be randomised to having a Prosigna test guided approach to their treatment or standard treatment. Path-for-Young is really the umbrella sort of putting all this together.”

“And it will be an international recruitment from Europe, from the United Kingdom and Australia will be participating in getting a large number, over 4,000 pre-menopausal women to really answer that question, can we select the women who really need chemotherapy and those that can be spared chemotherapy?”

“I think no one wants to have chemotherapy because it has a lot of side effects. Now, many of those side effects are short term, but there’s also some that are long term. And I think particularly for premenopausal women, the chemotherapy can have massive effects on things like their body image, losing their hair, but also the risk of early menopause infertility.”

“Often women are diagnosed with breast cancer when they’re in at a young age where they haven’t maybe completed their families or started their families. They haven’t yet found their sort of life partner. And I think having chemotherapy can really have a big impact on those things, and their ability to work and maintain their job. Chemotherapy can really make that difficult. I think for all women it’s important to try and make sure the people that get the chemotherapy really need it.”

“But I think particularly for those young women, if we can spare them some of these long-term risks and also those risks for fertility and early menopause, there’s benefits to be had.”

And how does OPTIMA Young differ from existing treatment approaches?

“I think the standard approach for young women with hormone receptor positive high risk breast cancer is that they all get chemotherapy and they all get endocrine therapy. There have been studies done looking at tests like the Prosigna test, predominantly in postmenopausal women showing that those women can be spared chemotherapy using one of these tests to select low risk. But we don’t yet have evidence that this is safe to do in premenopausal women.”

“And some of these studies have said that in premenopausal women, the chemotherapy is more important. What we don’t know is whether the chemotherapy benefit is coming from something the chemotherapy is doing in those young women or whether it’s related to the fact that many young women go into an early menopause from the chemotherapy, and it’s actually that early menopause that’s making the chemotherapy have the benefit in that group.”

So, Path-for-Young is being run in Europe and Optima Young is being run globally. Why is it important to have an international collaborative approach?

“To really answer this question, you’re going to need almost 5,000 patients, and no one country could do that. I guess in general, most breast cancer still happens in women who are postmenopausal. The premenopausal population with hormone positive breast cancer is a small group.”

“To get that 5,000 patients, To be able to really answer this question, it needs to be a joint effort. So, I think this Path-for-Young program is incredible how it is bringing together doctors and patients from across the globe. It is going to be Europe, it is going to be the UK, it is going to be Australia, and I think that’s going to be really important to help answer this question once and for all.”

How will findings from Optima-Young potentially change the way we treat young breast cancer patients in the future?

“So, if we can show that doing a Prosigna test can select the patients that need chemotherapy and those that don’t. This will become standard of care. So, a new patient that comes to see me with a hormone receptor positive breast cancer, rather than me saying you need to have chemotherapy, I can do a test on their tumor and say based on the results of this test, your cancer is high risk therefore, I think you really do need to have chemotherapy, or based on this test, we think you are not going to benefit from chemotherapy. You don’t need to have chemotherapy, and what we need to do for you is focus on the endocrine therapy.”

“I think it’s going to really make how we treat young women a lot more personalised and hopefully spare a lot of women the side effects of chemotherapy when they’re not going to benefit from the chemotherapy.”

“What I would like to see is better, more focused and personalised treatment and better ways to manage the side effects. I think the next challenge, if we do find that OPTIMA-Young can spare more women from chemotherapy, and therefore the main treatment is endocrine therapy, I think the next challenge is going to be what can we do to manage the side effects of that endocrine therapy to make sure our young women with hormone receptor positive breast cancer can lead the best lives and the best, have the best quality of life possible.”