How do you think ePRO remote monitoring could improve patient care compare to traditional in-person reviews?

“Yeah, so look, I mean, breast cancer is a varied disease, so patients are on all sorts of different treatments. For metastatic breast cancer we have some patients who are on oral therapies that are generally very well tolerated but they do sort of still have symptoms and other important issues that do pop up.”

“We also have patients who are on chemotherapies and also some targeted therapies like anti-HER2 therapies. So, patients can be on treatments for a very long period of time and remain quite stable. So, this project in particular is looking at whether we can improve the care of these patients who are on stable treatments.”

“So firstly, by earlier detection of symptoms and addressing these symptoms in a proactive manner rather than a reactive manner. Secondly, in terms of whether we can reduce the healthcare contact points, so perhaps having less frequent clinical reviews. We know that patients who have cancer, there’s an enormous time toxicity in cancer treatment and its sort of focusing on trying to reduce that.”

“We’ve got more patients living on treatment at the moment, and unfortunately, the number of patients who are on treatment is outpacing our workforce growth. We need to work smarter rather than harder on caring for our patients in order to live and continue delivering high-quality care to them.”

“We are very hopeful that we’ll be able to manage patients in the community rather than bringing them into hospital for assessments, you know, for admissions or emergency presentations. So, continuing to allow patients to be at home and doing what they want to do for more time.”

“In terms of barriers to this project, we love seeing our patients who are doing well. And so, one barrier to reducing those contact points is clinician satisfaction. And also, there is a potential impact on the relationship that we do develop with our patients if we’re seeing them less.”

“So, we really need to be careful about developing a system that appreciates that and maintains that human connection and contact, throughout their care.”

How do you think remote monitoring could impact a patient’s quality of life and their sense of engagement in their own care?

“Patients love to track. Everyone seems to love to track their symptoms, what they’re eating, and what they’re exercising on a daily basis these days. And I’ve certainly seen that in patients in the clinic. I think that designing a system whereby patients and clinicians are tracking similar things, and we are actually looking at the same values, and the same metrics to improve or to enhance sort of patient-centred care, is a great outcome.”

How do you foresee the cost effectiveness of ePRO being evaluated?

“Well, I mean, the cost effectiveness is a challenging thing to measure actually. It’s quite complex. On a basic level, we are looking at whether we can reduce those health service contact points, so nurse service utilisation, clinic visits, hospital presentations and admissions. But, in the future we will look to do a more thorough economic analysis in terms of quality-of-life adjusted years etc.”

“But you know that’s further down the road. You know, the first part of this project is certainly more about implementation of the electronic patient reported outcomes in the clinic.”

In what ways could ePRO remote monitoring reduce the burden on healthcare resrouces and improve system efficiency?

“I think the exciting thing about implementing patient reported outcomes in the clinic is making sure that we’re addressing the things that are important to patients. So, you know, often a patient might feel like, their doctor was running an hour late. They don’t want to bring up that thing that’s going to take 45-minutes to discuss.”

“Or perhaps they’re embarrassed to talk about some of the issues that do affect our patients with breast cancer. So, sexual dysfunction, emotional or psychological needs. And I think that patient reported outcomes really provides clinicians a way of ensuring that we’re addressing those needs that are really important to patients.”

“And hopefully we may actually see that we can do that in a more efficient manner as well. It’s a strategic importance to many organisations involved in cancer care, both in Australia and internationally as well. Patient reported outcomes have been incorporated into many guidelines internationally.”

“And certainly, our local organised cancer organisations are very keen to incorporate patient reported outcomes into routine clinical care. That implementation into routine practice has been varied across Australia and there’s a lot of work to be done on, on making sure that we are doing that.”

“We’ve got good data now across a number of tumour streams for monitoring symptoms and also monitoring health related quality of life.”

What are the current challenges faced in monitoring patients with metastatic breast cancer on systemic therapies?

“There’s a huge time toxicity involved in cancer care and in particular for women who have metastatic breast cancer who are on treatment for very long periods of time. And are often coming in and out of hospital for appointments has a huge impact on their life, and their ability to get on with doing what they want to do, especially for patients who live further away.”

“So, whether that be, outer metropolitan cities. Or even regionally as well using electronic or digital remote monitoring is really important. It’s an important strategy to try and improve the care of these patients and reduce the amount of time they spend attending their cancer clinics and care.”

What are the challenges or considerations when determining the best adjuvant treatment plan for a patient?

“When we think about what types of treatments to offer for patients, we want to consider a variety of factors. We want to think about the cancer stage, meaning how large is the cancer, has it gotten into lymph nodes? We want to think about the tumour biology, and that includes the hormone-receptor status, and the grade of the cancer. We also want to think about what’s driving the cancer cell, and what’s making it grow? And then the third feature we want to think about is, who is the person with breast cancer? What’s their health like? Do they have other competing health issues?”

“It’s also really important for us to consider someone’s personal preferences. What do they want to receive in terms of their treatment? And this is the work that the breast cancer specialist does with the patient to help come up with a personalised treatment plan. So I’m really excited to speak at this meeting about some of the new therapies that we have available for hormone-receptor positive disease.”

“One of the most important factors is a category of medicines called CDK4/6 inhibitors. These are pill medicines that are a targeted therapy. They’re not chemotherapy, they’re not hormones, but they’re their own special category. And they are designed to be used in combination with hormone medicines to help them perform better.”

“These are medicines that we use quite frequently if patients have recurrent metastatic breast cancer, and the idea is to use them earlier on in treatment to help prevent cancer from coming back and help cure a patient of breast cancer. Currently, there is one medicine that’s been approved in the United States called Abemaciclib, which is in frequent use for high-risk node-positive, hormone receptor-positive disease.”

“And there’s been a lot of research looking at other agents, which may also have benefit in this setting. So, I’m excited to cover this topic and talk about new directions for research in this area.”

“Another topic we’re going to talk about is the use of immunotherapy for hormone-receptor positive disease. This is a very specialised kind of medicine designed to stimulate our body’s own immune system to help fight the breast cancer. And we use this quite frequently for patients who have a different kind of breast cancer called triple-negative breast cancer, and we give this before surgery.”

“There’s been some very provocative data coming out in the past year looking at trying this strategy for hormone-receptor positive. And we’re going to think about how this might work and who this might be best for. And then a couple other topics we’re going to talk about are kind of emerging topics.”

“One of them is the idea of something called CTDNA. This means we can take a tube of blood from a breast cancer patient and in that tube find microscopic amounts of tumour DNA. And we can do this for people after surgery to try to establish how much risk they might be of the cancer coming back.”

“This is something we do in a research setting and we’ve seen now some recent demonstrations of how this might be helpful to establish what is a patient’s risk. But I think what we really need to figure out is if we find someone who’s at more risk than we initially thought, what do we do about it? What’s the treatment strategy? So, I want to think together about that.”

“And finally, we’re going to cover a very new emerging topic of a new kind of hormone medicine called oral SIRDS. And these are brand new medicines, mostly being studied in trials right now for metastatic breast cancer, but there are many large trials going on in the adjuvant setting that are beginning to explore these drugs potentially as a replacement for the kind of historic hormone medicines that we’ve had.”

“So, a lot of research, a lot of new discoveries. I think it’s going to really revolutionise how we take care of patients in this space. So, one thing I’ve been really impressed with working with the Breast Cancer Trials group is how much research is going on looking into the experience of patients receiving therapies in the adjuvant setting.”

“In particular, not just picking the most effective therapies and what’s going to help a patient the most but understanding the patient experience and how we can improve that, so patients are living long and healthy lives afterwards. For example, there’s great interest in how we take care of our very youngest patients, the young women who are affected by breast cancer at a time in their life when they might be starting their family or starting their career, and how can we help provide the best treatments while also maintaining things like fertility and allowing patients to have families after their initial breast cancer treatment.”

How can patients make more informed decisions about their treatment?

“So, I think for someone who’s been diagnosed with early-stage breast cancer, one of the most important things first is having a good relationship with your providers. Breast cancer teams around the world are so highly trained, and we work together as a global community to provide the best possible care for patients.”

“And so being comfortable asking questions, and you know, if you hear about something or read about something, bring it up with your provider. See what they think, bounce it off them. I think that’s really important. Also, none of the work we have available today, none of the important tools would exist without patients volunteering to be part of clinical trials.”

“Participating in trials is an immensely important way to help move the needle forward with how we take care of breast cancer patients. There are so many trials available around the world. Many of the most important trials going on are available to patients in Australia and New Zealand. And it would be so important for people to ask your provider, can I be in a trial? Am I eligible for a trial? What trials do you have going on right now?”

“These decisions that we make on an individual basis will have ramifications for patients around the world as we learn the results of these trials and we can optimise therapies. So, I really encourage people to ask about being part of research.”

What role does a patient’s hormone-receptor status play in the treatment of their breast cancer?

“When a patient is first diagnosed with breast cancer, it’s important to learn as much as we can about the cancer in order to optimize therapy. There are three major categories of breast cancer that somebody can have, and that’s defined by receptors that we test on the outside of the cancer cell.”

“There are the hormone receptors, there’s HER2-receptors, and then there’s also cancers that do not test for any of these receptors. Those are called triple-negative breast cancers. Learning which variety or subtype of breast cancer a patient has is one of the first steps that we have in understanding what are we dealing with and also beginning to think about how to pick all the best strategies.”

“Most breast cancer is hormone-receptor positive, HER2-negative. That’s about two thirds of all breast cancer. And that’s an area where there’s been a tremendous research focus on trying to provide really good therapies that help to optimally kill cancer cells but not expose somebody to too much treatment or too much toxicity that’s not going to be helpful.”

“I’d say one of the most exciting things that’s happened in the world of hormone receptor positive early breast cancer over the past couple of decades has been the use of genomic tools. We have a test called Oncotype, which is a test done on tumour tissue that’s removed either with biopsy or a time of surgery.”

“This test is really important because not only does it give us a little insight into the breast cancer tumour biology, but it also teaches us about whether a cancer is sensitive or not sensitive to chemotherapy. Not every cancer responds to chemotherapy. Not every cancer is sensitive. And we certainly don’t want to give that to somebody if it’s not going to help them.”

“And so, for the vast majority of people who are diagnosed with hormone receptor positive breast cancer, we do send these types of tests. And this really helps us better understand and select who the people are, in which chemotherapy will be helpful, and they should go for it. And then who doesn’t need it? Who can be spared that exposure?”

How important is international collaboration in breast cancer trials?

“I’m so delighted to be here in Australia meeting with my colleagues from around the world and in particular my very dear colleagues from Breast Cancer Trials.”

“The breast cancer community is a very tight global community. We come together for our meetings, which occur throughout the globe. And we meet frequently to design trials and lead trials and talk about patients. And in no way do we do this in isolation, we all work together. It’s incredibly gratifying to meet with my colleagues who work in places all over the world and find that our treatment patterns and our treatment decisions are very consistent.”

“The way we take care of breast cancer in Sydney is very similar to how we take care of breast cancer in Boston, or Vienna, or London, or anywhere. And so, this is very helpful because this means that we can run global clinical trials. Knowing that we can improve the standard of care in all of these places around the world.”

“So, it’s really exciting to be part of such a tight knit global community. And I think that also provides a lot of confidence for patients. That no matter where you are in the world, your doctors talk to other doctors in other countries, they attend international meetings, and the decisions that are made are decisions that are not specific to your clinic or your country, but these are the decisions that people around the world are making together.”

“So, I’m very much reminded of that when I come to visit with my colleagues, and I’m really just gratified for our international community.”

What are biomarkers of HR deficiency in breast cancer?

“Biomarkers of homologous recombination deficiency are tests, effectively, that you can apply to a tumour or to a patient, that help us understand whether a normal process of repairing our genetic code, our DNA, is faulty in the tumour development.”

“That is used as a way of identifying if those tumours might have an Achilles heel, a particular weakness that we can target with cleverly developed individualised and targeted therapy approaches. So those biomarkers are effectively a test that can be applied for a patient on them or their cancer that help a doctor decide how best to treat them.”

How does HRD targeted therapy work?

“What ourselves and others developed some years ago was an approach whereby inhibiting an enzyme usually used by cells to repair their genetic code and stopping it working, that could critically disable cancer cells that already had a defect in another form of DNA repair, something called homologous recombination, a very accurate form of DNA repair.”

“The normal cells of the patient could tolerate that drug stopping some of their DNA repair from working because they’ve got the backup, they’ve got this homologous recombination working, but the tumour cells could not tolerate the double hit on that. That’s the synthetic lethality concept.”

“So, the targeted treatment were PARP inhibitors, developed to target, create a particular form of damage in the DNA of the tumour cell that they couldn’t survive, but that the normal cells of the body could survive.”

“Hopefully this will have a big effect on cancer, with few side effects, and that’s proven largely to be the case. So, over recent years it’s become clear that although initially it was thought that the main effects of this type of approach would be in ovarian cancer and breast cancer known to run in families, and in those that had a genetic test saying they’d inherited a faulty BRCA1 or BRCA2 gene, it now seems that this applies in other forms of cancer associated with faults in those genes, like prostate cancer and pancreatic cancer to name two.”

“But also, that people who haven’t necessarily got a damaged gene running in the family, but where the cancer itself, but not their family, the cancer’s got a damaged copy of the gene. And that means it’s potentially applicable to a larger group of patients suffering with cancer.”

“We need to develop those tests better, that tell us if that’s truly the case in the cancer. We also need tests that tell us is it not a gene that’s faulty? Is it maybe that the dimmer switch on the gene has been turned down, as it were? The gene’s just not turned up full, it’s silenced, it’s dimmed down. And whether patients with those kinds of cancers could benefit too.”

“So, it’s a work in progress.”

What are some of the challenges faced by researchers in understanding a predicting the emergence of resistance to HRD targeted therapies?

“So, there are still big challenges for patients who have these kinds of cancers. I think the field has made a lot of progress and thankfully these treatments are now available for people with quite early cancers of those types like breast cancer. And that is curing patients, which is fantastic news, but sadly some patients still develop advanced forms of cancer where it’s not possible to cure or eradicate the disease. And eventually, the disease becomes used to these treatments, and it becomes resistant to them.”

“So, the challenge is working out how it becomes resistant, how it learns to cope with these apparently very targeted drugs and then realising that there’s not one way of becoming resistant, and then designing treatment approaches that deal with each of, what may be a few ways in which the cancer gets around.”

“And that’s what everyone’s trying to do at the moment, understand that. Not just what happens in the lab, what can happen for resistance, but what happens in the clinic for patients and designing the treatments that help them.”

What is the role of research in hormone therapy resistance?

“So, the role of the researcher and of research in doing this I think is manifold. We need to work with and involve our colleagues in what we call basic science. It’s not basic at all, it’s kind of fundamental science, that’s a better word for it really, to really understand the biology behind resistance and that’s often work in a lab with white benches and pipettes and clear colourless fluids and plastic dishes, but it’s very helpful.”

“It’s very contributory, connecting those with the real questions that doctors have working with patients who are, who are suffering with these diseases, so that the power is applied to real problems in the clinic. That is the opportunity for what we call translational research.  And when you bring those things together, that’s why I get out of bed in the morning.”

“It’s suddenly some really meaningful conversations that happen because the fundamental scientists go, ‘I didn’t really realise that’s the problem you’re trying to solve’. And the clinicians go, ‘I didn’t realise that you could do something that could solve that problem’. And then they talk and then they redesign and then stuff happens.”

“It’s really exciting to see that happening and try and make that happen. So, what we then do is we ask our patients, would they join us in that endeavour? Which of course they do. And we can then ask if people would contribute an extra blood sample, let us study the tumour that they had removed at surgery and is sitting in a pathology department, but not being used.”

“We ask them if we can study that tumour deeply. Could they maybe have an extra biopsy? And could we take that into the lab and grow cells and do some of these very clever techniques on the living tumour, to learn how to get around the resistance and that is the research. That’s the challenge. That’s the opportunity. That’s the translational research endeavour.”

Why are the BRCA1 and BRCA2 gene mutations significant and how do they relate to targeted therapies?

“The BRCA1 and BRCA2 gene mutations, which are a large part of what I’m talking about, are very significant because they were found to be the genes that when a fault developed in them and could be inherited through generations, were responsible for the majority of the admittedly relatively small group of women who have very strong family history of breast and to some extent ovarian cancer.”

“Most breast cancers happen for reasons that we don’t fully understand. They’re more complex than just inheriting a gene or living your life in a particular way. They’re a really complex mixture of all of the genes that we might inherit and some environmental or lifestyle factors.”

“But some are due to an inherited gene fault. BRCA1 and BRCA2 were the main causes of that strong family risk. The field have identified some other genes, a gene called PALB2 being one, that are also responsible for this to a slightly lesser extent. But they all seem to operate, these strong genes, in this way in which cells keep their genetic code accurate and clean and stop it developing missed messages, that then tell the cancer cell run wild.”

“So BRCA1 and BRCA2 have been so important because they’ve led to an understanding of how breast cancer can develop and provided an opportunity to develop a targeted treatment approach, even for a rare group.”

“And I think that’s helped the whole field understand that you don’t just have to work out the common causes of cancer. You can find the rarer causes and then develop individualised approaches for them. And then find they’re actually important for a bigger group than you thought to start with. It’s taught us to care about individualised medicine. BRCA1 and BRCA2 have provided an example of that.”

What is synthetic lethality?

So, synthetic lethality is an old genetic principle, taken to an individualised medicine context, and leading to a way of identifying through a biomarker, effectively a test, a group of patients who would benefit from a targeted approach with profound effects against the cancer and few side effects in their normal self.”

“So, the excitement in the field around this are that although perhaps the poster child for synthetic lethal targeting principles has been BRCA gene faults and PARP inhibitors as the other drug partner in the synthetic lethality mix. It’s meant that cancer researchers have begun looking for other synthetic lethality opportunities, and some feature of a cancer that means that if you find the other partner, you’ll have profound effects that are restricted to the tumour.”

“And so there are other examples of that which are emerging in the field of this form of homologous recombination defective breast cancer.”

“We know that other DNA repair enzymes are being investigated. Biotech’s and drug companies are developing strategies specifically to target DNA repair enzymes in order to follow the same path that has been followed by this poster child of PARP inhibitors and BRCA. And there are a number of examples of this.”

“I won’t pick a particular one to favour any particular biotech or pharma, but there are a number, and it’s exciting. And then outside of DNA repair, there are other examples of synthetic lethal targeting as a concept.”

What does the concept of team science mean to you, and why is it so important?

“The power is so much greater, given that we’ve got so many disciplines of science, so many different kinds of cancer that our patients are suffering from, that we have to do this as a team, in order to make a difference.”

“And our chance to make a difference is so much greater as a team. So, what does team mean? Team means communication between patients and their doctors and the scientific community, to really set out what is the problem we’re really trying to address here, not what is the sexiest piece of science, but what is the problem that we need to address and how can we bring the power of science to it?”

“It’s genome scientists, people who are using the amazing power of understanding the human genome, all the messages it creates, all the proteins that those messages lead to, the complexity of biology, which then requires you to have really highly integrated computational systems to bring that together.”

“The power of AI in enabling all of that, and then there are always new developments in how we test things in a laboratory, how we develop an idea that can test it. So, people may have heard of CRISPR/Cas-9 methodologies, where you can edit the gene. And therefore, the message and the protein that it produces in an incredibly accurate way in the genome.”

“Combine those edits to test things before they even get to needing to experiment on an animal or a patient. And the power of doing that is enormous. Bring all of those together, get people communicating and show them the problem and iterate. Bring it round in a circle and stuff happens and it’s amazing.”

What steps are taken to ensure that targeted breast cancer therapies are safe and effective for patients?

“So, there are obviously a number of steps that need to be taken to ensure that ideas around a targeted therapy are real, work, and that they’re safe and should be available to patients. Those, steps really are the validation as we call it in laboratory settings, that someone’s idea can be repeated by other people who are perhaps less invested in it having been a good idea.”

“So independent validation that what’s been found is real. And across multiple sorts of experimental systems, it’s not all just coming out of one laboratory way of asking the question. And that gives you confidence that there’s something real to take forward.”

“Then you really need to understand whether the treatment approach, or the therapy approach works in a clinical environment on patients. And before you do that, you often do need to go through testing things in patient materials. And that now can be with growing little tumours in little organoids, which are like little greenhouses of culture material. They’re more like the flat plastic things are often grown on in the lab.”

“And that is a bunch more real connection with what happens to patients’ tumours in the clinic. So that’s a step of validation in the lab, not yet in the clinic. And then they go sometimes through an experiment in a mouse to check that’s true towards clinical trials. Those are called phase one clinical trials, just checking that a drug approach is safe and what some of the side effects are that might be associated with the dose that’s actually getting to a right level in a patient and hitting the target properly, phase one.”

“And then we call phase two trials, those trials where you’re looking to get more confidence with more people, that the dose you selected in phase one is not really associated with side effects. And there some evidence it works.”

“You know, does someone’s tumour get smaller? Does it respond? And then beyond that, things that have been through that stage are really asking the question, how does it compare with the treatments that people already have available, if there is one, and how are you sure, for instance, that the effect you’re getting isn’t a placebo effect, just because someone’s reporting they feel better.”

“And that means having trials where you randomly allocate treatment, new treatment, against the best we have, and blind the doctors and the patients taking part to what they’ve had so that we can be really sure that this is going to work. And you might say, well, why be really sure? If it sounds good, just do it.”

“Well, we’ve got to be really sure because there’s always some kind of alternative that you’re taking away from someone if you’re giving them something new. So, you need to know that it’s better and the side effects you’re going to confidently tell your patient you think they might get.”

“Those phase three trials are really, really important. And the tests that you use to select patients for a targeted or individualised treatment approach need to go through that same process of validation, of checking that they work in the lab, that they’re accurate, repeatable, that they mean something clinically meaningful. That’s called clinical validity and they help a doctor advise a patient and make a better treatment choice..”

“So, it takes a while to get that right, but people expect that when a doctor sits down with them and advises them on a treatment based on a test that selects a treatment, they’re confident that it’s going to work and not cause them problems. That’s how we get there.”

“It’s important to say to your doctors looking after you, is there anything different for me because of this? Are there treatment approaches that are especially for me?”

“Because there are some. It’s difficult to summarise those here, but they apply in both the early breast cancer, the sort of curative environment in breast cancer, and also in those who’ve got secondary breast cancer, where sadly the disease is not usually considered curable, but where there still may be individual approaches for those with these mutations.”

“Also asking are there clinical trials for them? Because the trials have been developed now to take things forward specifically for this group of patients. So, it means asking the question about what may be special for you. And also, you know, considering whether if there isn’t something in your local hospital, nearby or in a more specialist hospital with a strong connection to your local hospital, there is something for you there.”

“So, I would say it means asking about individualised medicine for you. There are other things to think about, like any effects there might be on risk for the future. If you’ve just been diagnosed with an early cancer and you may be thinking about risk to your other breast. So, these are things that you need to talk to your team about and have the time to process the information and also the implications for family.”

“But I always say to people, you don’t need to make all the decisions instantly. Talk to a specialist team and take time to make the decision.”

What excites you the most about the future of breast cancer research?

“I think I’d have to say it’s the fact that there are now so many more conversations happening between patients, their doctors, and a demand to do research. To be involved in research as a patient, to be given the opportunity to consider a trial or just consider contributing maybe a little bit of extra blood or, or your previous tissue in the pathology department or have an extra biopsy to try to move things forward.”

“There are so many more opportunities for doing that. The medics are talking to the more fundamental scientists in the lab about doing that, and that there are people trained to bridge between those disciplines. Medics who’ve spent time in the lab and have learned enough to have a really good conversation about it and how much they want to be involved and help.”

“And that happens so much more now. There’s a real opportunity for us to bring this together and develop new treatments. And we do that in partnership with the biotech and pharmaceutical industry. But there’s a real contribution that patients, their doctors and the fundamental scientists can make to how biotech and pharma develop drugs. And they know that. And I think that is also changing and leading to more smart individualised medicine, and effective therapies being developed.”

What is surgery de-escalation?

“Well, historically breast cancer surgery was amputation. Basically, we have moved from there to breast conservation as the gold standard of care. I think that’s still an important goal in addition to providing care for our patients.”

“Obviously, we want to succeed in preserving their physical integrity as much as possible. And for the surgeon, that means preserving the breast. I think strategically, we have learned a lot, both in terms of surgical technique, but also in terms of changing the order of treatments, such as bringing the medical treatment before the breast surgery itself shrinking down the tumour, thus enabling breast conservation in situations where previously mastectomy would’ve been the case.”

“But I still believe it’s an important goal to eliminate mastectomy eventually. When you ask patients before their treatment, what do you want the outcome to be? Obviously their first thought is ‘I want to be cured’. And fortunately, we can achieve this nowadays for the majority of breast cancer patients.”

“But in addition, we want to keep our treatments as acceptable as possible. That means side effects need to be controlled and impacts on quality of life need to be alleviated.”

What are some examples of surgery de-escalation in breast cancer?

“Examples of surgical de-escalation, in addition to like moving from mastectomy to breast conservation as a standard of care, mainly means in recent years the different treatment of the axilla, under the armpit. There are lymph nodes that used to be removed for diagnostic purposes, which historically had some adverse effects like lymphoedema, which is swelling of the arm which can impair our patient’s quality of lives for good.”

“And we have moved away from doing that to a more selective approach where this is called the sentinel node procedure. So, we just take one or two nodes, check them under the microscope. If they are okay, then the remaining lymph nodes can stay in place.”

“Meanwhile, even in some situations where certain nodes are affected by the disease, we have developed techniques and strategies, to leave the axilla alone to avoid surgical complications.”

How are treatment decisions made with both the patient and the treatment team?

“Having said this, obviously it sounds a little bit easier than it actually is. There’s a lot of confusing information out there. I mean, when you Google or use social media, you will get all kinds of information without knowing what is accurate, and what is not. So, I think it’s good that we have informed decision making nowadays with multiple sources, but it eventually doesn’t take away the need for a trusted caregiver.”

“At some point, even when you do all your research, most profoundly, you will have to trust the caregiver who tells you this is what I believe is the best situation for you. Or sometimes there might be two or three options, and here are the advantages, here are the disadvantages, to help you make your choice.”

“That needs time that in reality is not always available. So, I think healthcare systems need to keep in mind that if we want to achieve that, and everybody talks about shared decision making, we also need to provide the necessary resources in terms of caregivers’ time. And that’s a challenge in many places around the world.”

What are the primary goals of surgery in managing breast cancer?

“Well, I think that the goals of breast cancer treatment in general are curing the disease, preservation of quality of life, and eventually just getting rid of the problem. And that’s fortunately possible now for the majority of people affected by the disease, which is quite different than the perception and expectation.”

“So, I think one of the most important jobs that we have, particularly in the beginning of the interaction, is to take away the panic, to try to alleviate the fear, to be realistic on one hand, but also optimistic because there’s a reason to be. Clinical research has helped in the last two decades, both in my country as well as in Australia and New Zealand, to cut back by at least 25-30% of the mortality of the disease.”

“The majority of patients being affected with breast cancer nowadays will die from something else, which is the ultimate definition of cure, from our perspective. So, I believe that finding that balance between, yes there is a problem, we need to do something, we need to be mindful, but also, yes it can, for most cases, be resolved.”

What research has been done in this area?

“I think the main advances of surgery is both in the technical field, there is advances in the surgical techniques in terms of strategies, conception, but probably the implementation of a strictly interdisciplinary process.”

“I remember having a patient about 25 years ago and she said, I had a dream, and the dream would be that all the experts of the world come together and discuss my case. And then they would find the optimal solution for me and suggest it to me. So, I keep thinking of her because actually that’s now reality.”

“You have the experts of an institution, involved in national and international case discussions. We have guidelines and recommendations, that are moving the field forward. In addition to all the advances in individual disciplines, such as surgery, medical oncology, radiotherapy, I think the main progress has been made that these people now on a regular basis discuss every patient.”

“They optimise and individualize the treatment approach, which may mean that surgery is not the first step. We may start with some infusion treatment for six months, shrinking the tumour, rendering the surgery much easier. I think that’s what we have learned recently.”

What is the role of the axillary lymph node dissection in breast cancer treatment?

“It’s important to realise that historically the axilla was treated with curative intent. So, removing disease that sits there. Now that has changed, not in all cases. There are still situations of locally advanced regional breast cancer where that aspect is still there and needs to be done.”

“However, as a diagnostic procedure. The invasiveness of what surgeons are doing under the armpit has been massively reduced. Reducing axillary dissection to sentinel node procedure, maybe even not touching the axilla in selected cases, that’s a very new development and needs to be applied in clinical practice with caution.”

“But we see some data that not everybody necessarily may need axillary surgery. However, it’s also kind of a fashion to de-escalate and we need to be mindful that, for example, the number of lymph nodes affected by the disease could offer important information in helping to tailor the individual’s adjuvant treatment.”

“So, it’s always important to find a balance between, the fashion trend, which is de-escalation, whilst also maintaining what is necessary for an optimal treatment decision.”

What’s been the primary evolution in this area?

“Traditionally, the concept was when the central node is negative, that’s it. When the central node is affected, there will be a full accelerator section. That has changed recently. Nowadays, if there is limited involvement of the central nodes, one to two accelerator nodes. Accidental dissection may not be a necessary unless there is additional information important for further treatment decisions.”

“But we are testing these concepts in the context of clinical trials, which is always important because just having a nice idea is not good enough if you want to change standard practice.  We obviously have to prove that this is beneficial and without harm at the same time. With respect to alternatives to axillary node dissection, there have been trials demonstrating that radiotherapy can also do the job in controlling the disease.”

“Personally, I have to say I’m rather critical of that substitution of surgical techniques with radiotherapy while acknowledging that disease control would be the same. If we leave the lymph nodes in there, we don’t have the information whether they are affected or not. So, I think it’s important to understand that disease control, yes, radiotherapy to the axilla might be equally effective compared to surgery.”

“But when I remove five nodes, and I know two out of five are affected, that’s important information for the treatment decision. When I just irradiate the axilla, I don’t know if that’s one node, two nodes, or even five nodes? So, I missed that information.  with all the hype about surgical de-escalation, we need to be careful not to de-escalate surgery too much and then compensate with the escalation of radiotherapy.”

“As a matter of fact, modern breast cancer radiotherapy is also de-escalating, and reducing from five weeks to two weeks down to five days, maybe not having to irradiate all patients. So, I think it would be unfair to abuse, so to speak, radiotherapy to compensate for insufficient surgery.”

Are there specific breast cancer diagnoses where ALNDs are still relevant?

“I think with all the reduction in the frequency of ALNDs we are doing, we need to realise when there is Crohn’s disease, when there is symptomatic disease. Unfortunately, we’re still not catching every situation early enough, and in those cases then yes, there is a role for curative axillary dissection. Having said this, in a locally advanced situation nowadays, we usually start the treatment with medical treatment, because that has been proven effective.”

“We want to reduce the extent of the disease before tackling it with local regional treatment.”

What are the main advancements or excitements around de-escalation and improved surgical techniques?

“I think in terms of the future, we will see further improvement in our ability to tailor the treatment approach to the individual. Yes, we might find situations occasionally where we can avoid surgery altogether, which is a little bit like a fashionable goal from a patient’s perspective. But actually, that’s not a high priority. I mean, breast surgery nowadays is almost without complications and can be done on an outpatient basis in many situations.”

“As for surgery, as for radiotherapy, as for medical treatment, further individualisation is the most important priority for the immediate fruit of future.”

How do you work out who will be a good candidate for volume replacement surgery?

“Look, that’s a really good question. So, in the primary breast cancer scenario, we have women with either very extensive breast cancer where the volume of the actual cancer removal is quite large in comparison to the volume of the breast.”

“Often women with smaller breasts, where there’s less drop to the breast, that sort of thing, they’re the ideal candidates. And especially if they’ve got a little bit of spare tissue around the sides or underneath the breast, where we can then transplant that tissue and move it into the breast.”

“So, we rebuild the breast by removing tissue from outside and around the breast, or indeed other parts of the body using the fat, as I mentioned. So again, it just reduces the rate of women having to undergo very complex breast removal, mastectomy, and then more complex reconstruction procedures.”

What are the benefits of this procedure?

“These women will need to then undergo radiotherapy to the breast generally as part of the overall treatment, and possibly other treatments as well, drug treatments. And it just means these procedures are all day surgery treatments, so they’re in and out of the hospital in the same day.”

“The recovery is very quick. They’re relatively painless compared to some of the more extensive procedures, and they wake up with a pretty good cosmetic outcome. You might say, well, why not just use a breast implant for reconstruction? That’s pretty simple too, and sort of overnight hospital stay.”

“But breast implants will cause more general problems, complications, infections can happen. And there’s always some ongoing maintenance with implants. Whereas this is pretty well a one-step procedure, that’s robust and will last a long time, because it uses the patient’s own natural tissue, so that’s the key.”

“So, in fact, I know we do reconstruction using the patient’s own tissues, from the lower abdomen, the tummy tuck, if you like, or from the thighs or around other areas of the patient’s body where you can move bulk tissue. This removes tissue and replaces it just from around the breast.”

“So, it’s in the vicinity of the breast, so the downtime for the patient is much less. For example, with the tummy tuck procedure, these days, hospital stays are getting shorter. So, there might be three to five days, where there used to be seven to ten days in hospital. But often they can’t do heavy lifting, they can’t run and get back to their normal daily activities for probably six weeks or so.”

“Whereas with this procedure, they might have a little bit of restriction in their shoulder movement with the arm on that side for a couple of weeks. But, because we don’t use muscle in the procedure, that recovers very quickly. So, they’re not losing power or strength and generally, recovery is quick in comparison.”

“There are always risks with fiddling with small blood vessels. So, it does take training and we’ve done a sort of global study looking at training needs. This is probably considered a more advanced procedure for the breast surgeon. And so, we’re doing a lot of workshops to train people in the technique, so it becomes more widespread.”

“It’s certainly available in the larger centres around Australia as well and so it’s just a matter of asking, you know, what the options are and who can do this. Usually in one centre there’s at least one or two surgeons that will undertake this. Yeah, so probably about one in two hundred risks of part of the flap or the tissue dying off.”

“That can happen before or even after radiotherapy because radiotherapy will always stress the tissues. And so sometimes patients end up with a little area of hard tissue. Now that can happen with any breast reconstruction procedure using the patient’s own tissues. But it’s relatively easy to treat.”

“It can be a bit painful, but you can suck that out through liposuction or even local anaesthetic, and you can replace it with new fat from around the body. So, it’s pretty treatable and there shouldn’t be many complications.”

“Yeah, so I think particularly in the realm of fat transplant or what we call fat grafting or lipo-filling, these are all synonymous terms. Many people have heard of liposuction, which is a cosmetic procedure for some patients who want to get rid of sort of unsightly or excess fat in the body.”

“This now takes that procedure, which is quite a traumatic procedure if you’re just removing it. But we’ve adapted the procedure over many years, and there are several machines developed for this. Which actually treat the fat super gently. We remove it in a very gentle way because this fat is literally like liquid gold now, we want to put it back to make sure it survives, and we traumatize it as little as possible. The body basically will sort re-adapt itself to take that fat on board, and then new blood vessels can be formed, and the fat then regenerates.”

“It’s shown to also improve the tissues after radiotherapy, which damages the normal tissues, and so it can reduce scar formation and tissue distortion after radiotherapy, so it’s a great procedure.”

“Alot of people are using it in many different cases, not just with breast conservation, but even over breast implant reconstruction. We’re even reconstructing whole breasts using fat grafting. The downside of fat grafting is you need to do multiple procedures, although each procedure is about 60 to 90 minutes. But you often need to do a repeated procedures a few months apart. So, it’s a process.” It’s often not one single procedure unless it’s just a tiny cosmetic thing you want to fix. But really, this is part of regenerative medicine and it’s a very exciting area. So, I think that technology is going to only improve with time.”

“To say that with the lipo filling fat transfer aspects of it, we are using what we call stem cells. The fat tissue in our body has an abundance of stem cells. In fact, maybe most of the body’s soft tissue stem cells are actually found with the fat. And so, we know which part of the tissue that we take out when we take fat out through these small needles.”

“One of the advantages is the scars are very tiny because we use two, three, four-millimetre needles to harvest the fat. But part of that fatty tissue is what we call the adipose derived stem cells. And those stem cells, if you just inject those back, particularly just under the skin, can rejuvenate scars, they reduce further scarring and they can make the body tolerate much more trauma, like radiotherapy and other issues. And it lasts a long time as far as we can tell.”

What is the role of the patient and how can they keep informed about their treatment?

“Yeah, it’s a really good question because I mean for breast surgery in particular, we talk about the concept of shared decision making. And this is exemplified in breast cancer surgery because, I mean the very initial decision is sort of mastectomy, removing the breast versus keeping part of the breast and conserving the breast.”

“This was something that was established years ago that either alternative is as safe in terms of the cancer outcomes. And in fact, we have a lot of data now, probably over a million patients, although it’s sort of data looking back at large patient databases. And we are asking maybe it’s even safer to not remove all the breast tissue.”

“This is something we’re a little bit circumspect about, but we know it’s at least as safe to keep some of the breast and perhaps there’s some immune local and microenvironment in the breast tissue that we left behind that might even protect the patients against cancer cells going to other parts of the body and setting up camp in different sites, which is obviously metastatic disease, and that’s what we’re trying to prevent.”

“So, there are some signals that that might be beneficial, but in terms of overall shared decision making, we’re really just trying to help the patient make decisions depending on their own priorities. So, if their priority, for example, is to have chemotherapy, as soon as possible after surgery, because that’s really important for their disease control and prevention of further disease, then we want to get them, get them recovered as quickly as possible, get them out of hospital as quickly and get on with their lives.”

“Some women have young children and so they don’t want to be burdened by a big abdominal scar where they can’t carry their child for several weeks. With some of these other procedures they can immediately use their arms, do lifting, that sort of thing.”

“So, there are many different aspects that we need to tell patients about. Again, depending on what they do with their arms and hands in their occupation and life, sort of the general lifestyle, we try and guide them as to what might be the best thing. At the end of the day, the patients will try and choose and trade off what works for them the best in the long run.”

“Often, you’ve got to guide patients a little bit because they’re initially so scared about the cancer. Often women will come and say, look, just chop off my breasts because, you know, they’re in total shock.”

“But we’ve got to look forward. Survival’s so good nowadays that we’ve got to look forward to survival issues. And we know that as women go forward one, two, three years beyond their surgery, they’re going to be more concerned about their aesthetic outcomes and their functional outcomes. So, this is really important to try and bring the patient back to that scenario early on.”

“Whilst you’re of course treating the cancer in the optimal way, you want to improve all those other outcomes for the longer term as well.”

“I want to mention the lymph nodes in the armpit, just for a moment if I could because it’s such an important area. It’s probably, arguably, much more a morbid issue than the breast itself for many patients because they can get lymphedema of the arm, shoulder stiffness, pain, and all that sort of issue.”

“I’m involved with a couple of trials including one based in the UK, called Tadpole, that’s sort of still in development, but coming along soon. We’re going to randomize patients between what we call a targeted axillary dissection, which is this removal of two or three lymph nodes, when one or two lymph glands are involved, versus taking all the lymph glands to try and prevent that sort of knee jerk reaction of taking all the lymph glands when often it’s just one or two that need to be removed.”

“So, we’re trying to refine that surgery better. And then on the other side, there is a worldwide trial called Sentinel 2, led from Sweden by a colleague of mine. And that’s where we use a particular magnetic liquid that we inject at the time of surgery for pre-cancerous change.”

“In about a fifth of those patients, they’ll come back with actual fully formed invasive cancer where we then need to go back and remove one or two lymph glands. And in this patient cohort, we never know up front whether we should remove the lymph glands, because what if we find invasive disease? Whereas with this, the actual trace that we inject at the time of initial surgery marks the lymph glands for one or two months even.”

“And so, we can then avoid taking the lymph glands if they don’t need to be taken. The pathology comes back as invasive cancer. We can then go back selectively in those 20-25% of patients and just pick out the one or two lymph glands there.”

Where do you see research going in the future?

“I think in general, the first thing is to raise the level of technical ability for surgeons, so that we increase what’s on their tool belts, to give patient options like the reduction of the breast mammoplasty, as well as volume replacement techniques, which originally were thought to be more plastic surgical treatments.”

“But often, especially in Australian remote areas, patients don’t have access to plastic surgical resources as much as they might, in the big cities. And so, it’s really important to equip surgeons to offer these various options.”

“That’s one thing. And on the other hand, I think with the armpit surgery, to try and just reduce the extent of armpit surgery. Many of us still feel very twitchy about leaving lymph glands behind because we think somehow the cancer’s going to come back, whereas we know it’s really just, if you like, a surrogate marker of the potential for cancer to go to other sites.”

“We really believe increasingly that the lymph node is not the source of the spread to other body sites. It’s more that it’s just a marker of risk. And so, we need to just remove the involved lymph glands obviously, but we don’t need to remove all the lymph glands. So, I think many of us are doing this already, but I think if we can just spread the word and make sure that treatment’s more homogenous across the board, doing less for patients, I think the patients will benefit just by reducing the morbidity.”