Jenna Dean is a radiation therapist at the Olivia Newton-John Cancer Wellness and Research Centre with an interest in patient-centred care, research, breast planning, and particle therapy.

This is the third year of the Breast Cancer Trials Clinical Fellowship program and Jenna has been successful in receiving a fellowship in 2024.

Her project is called OPRAH MRL and will investigate the benefits and limitations of lying on your stomach versus lying on your back during treatment with the MR Linac, a magnetic resonance imaging system integrated with a radiotherapy treatment machine, to see which patients will benefit more from either treatment position.

We spoke with Jenna about her project and what she was hoping to achieve through this research.

“So, I’m working on my own research but I’m also helping my colleagues in our department to build their research capacity because a large part of what we do, particularly when it comes to improving what we do for our patients, comes from the research that we do within our department.”

“So it’s really important that we all know how to conduct research properly, that we understand why we’re doing it and what we’re setting out to achieve, but also that we learn a lot from it, so that when we get those outcomes from the research that we do, we can apply it in a safe way to make things better for our patients.”

“Early breast cancer is the most common presentation at cancer diagnosis in Australia. I think last year they were predicting around 20,000 Australian women would get diagnosed with early-stage breast cancer. For most of these patients, they can have a combination of treatments, but most commonly they’ll have a surgical procedure where they’ll have the lump removed and then they will have treatment with radiation therapy a few weeks later.”

“For a lot of patients there’s a lot of the unknowns. So certainly, before I got into the profession, I didn’t know what radiation therapy was, so there’s some uncertainty there. There’s a lack of information for people from credible sources, which I think is really important, and there’s a lot happening in that space to improve that scene.”

“For a lot of patients, to have a course of radiation therapy, you can be coming in for treatment for up to three weeks. So that’s three weeks where you’ve either got to juggle work, or kids, or school runs, or just being away from home, and not being able to work your usual hours, so there’s a lot to consider there, and it’s also just that it’s tiring to go in for lots and lots of appointments.”

“So, we know that for breast cancer patients, particularly early breast cancer patients, that it is safe and effective to treat them in five treatments instead of over three weeks. We know that we can treat the whole breast with a patient lying on their back or lying on their tummy. And the reasons that we do that is it changes some of the anatomy inside around a little bit by treating them on their back.

“For some patients that’s more comfortable, but for other patients, if we can treat them on their tummy, then we can change the position of the breast and move it away from things like your lung and heart and still get a high dose where we want it but minimize the dose to the other position.”

“Now, both positions are perfectly safe, and we do everything we can to limit the doses to the structures that we don’t want the dose to go to. But logically when you look at the anatomy, changing that position can change how we approach things.”

What is Accelerated Partial Breast Irradiation?

“Accelerated partial breast irradiation, as it sort of implies, is delivering it faster. So that part of the treatment is that we deliver a bigger dose per treatment. So, for traditional radiotherapy, we will always deliver it over a number of doses. It’s a bit like a course of antibiotics. So, you take the whole course of treatment, and it builds up to the dose that we want as a total.”

“For the accelerated part, we’re going to give an equivalent dose, but we just give it in a smaller number of treatments, and we have a gap in between, so that the body still has a chance to recover and work the same way as it does with normal radiation.”

“For early breast cancer, we can treat the whole breast, or we can just treat part of the breast. And the reason that we’re moving closer towards treating part of the breast, is it then means that some of those longer-term side effects from treatment, like the cosmetic outcomes and some of the changes to your breast tissue are not as prevalent if we’re only treating part of the breast because the radiation only affects the area that it’s actually treating.”

“So, we do a faster course to a smaller area, and then in a shorter number of treatments. So traditionally you’d look at sort of 15 treatments over 3 weeks, but with the accelerated partial breast you’re looking at 5 treatments over a week or a week and a half.”

“With the way that the magnetic scanners work, the images are most precise in the middle. So when we set up a patient, because of the nature of the anatomy of the breast being sort of off to one side or the other, it’s not as close to the middle of that imaging field of view that we’d like to see, so where we look at the picture. So, because of that the changes in positions for these, like partial breast patients, could be affected by which position the patient is in.”

“So, if for example a woman is laying on her back, then the breast might fall out towards the side, and that moves it further away from that imaging centre. And in opposition to that, if we’ve got the patient on their tummy, hopefully that brings the breast closer to the middle of the imaging view. And it then hopefully it will result in fewer adjustment to that image.”

“Now, there’s lots of algorithms and fancy things we can do to the images to correct for this. But again, ideally, the more we can minimize it when we’re actually collecting the images, then the more assured we can be that we’re getting an accurate representation of what we’re looking at.”

What is the Difference between a Supine and Prone Position?

“So, in a supine position, the patient’s laying on their back with their arms up above their head, and fairly flat. But in the MR space, we also then need to use another part to take the picture, which means we’ve got a big panel that’s referred to as a coil that comes quite close to the patient’s face.”

“For some patients that can actually be quite confronting and a little bit scary. So, lying on your back, you’ve got arms supported, but it’s the best way for us to get access to treating that breast and not treating anything that we don’t want to treat. If we were to treat somebody prone, that’s putting them on their tummy. We’ve got a specially designed board that allows us to have the breast we’d like to treat sort of hanging in a space, so it moves down towards the treatment machine.”

“The other one’s sort of up and off to the side so it’s well and truly out of the road. And it’s a bit like lying on a massage table. You’ve got your face in a little hole so you can see there’s still air there, and again, you’ve got both arms up, but it’s kind of like you’re just sort of lying on a massage table with your arms up. But again, it just sort of flips all of your anatomy over.”

“So, my project is looking at the differences with that, as well as sort of the changes or potential changes to the image with the field of view and where the anatomy sits in that space. We also know that by treating part of the breast for some patients with their tumours, depending on which part of the breast it’s in, for some patients we hypothesize that it’s going to be better to have them treated on their tummy because having the breast moved away from the chest wall is going to help us get access to that tumour there.”

“But for other patients, if it’s up really high on the breast or really close to their middle, then that position can actually be quite challenging. So, the idea is to get each of the patients to lie in each position and see which one would be better for them based on where their tumour was because they’ve had surgery before they come to us, and then where it then sits in relation to their other anatomy.”

“So, we’re going to take lots of measurements and try to work out which position would be better, if a patient has a breast tumour for example towards their middle on one side, or out on the outside. Hopefully we can use that information to work out whether dose wise or comfort wise they would be better in either position.

“So, we do intend to ask everybody who participates in the study whether they preferred one position over the other, and also get them to let us know why. So again, we can sort of include their feedback because the board was developed so that we could actually set up this study. There wasn’t a version available prior to this. So, we’ve sort of based it on what we think and our clinical experience, but to also get some patients actually using the board and telling us what they like about it, telling us what could make it more comfortable.”

“So those original scans, we are sort of looking at 15 to 20 minutes in each position. The treatment takes a little bit longer because the beauty of treating them on the MR machine is we can take an MR picture. We can see exactly where everything is without giving them any radiation. We then have it set up in our system that we can see what’s changed, and if we need to, we can make some adjustments to the treatment plan before we deliver their treatment on the day.”

What are the Research Methods for this Project?

“So, this one’s a pilot study from our perspective. We want to see if it’s feasible and we can treat patients with the board because some of the studies in Europe had sort of suggested that treating patients in that position on their tummy wasn’t actually possible just because of the size limitations with the MR Linac.”

“We’re hoping to show that we can actually deliver it that way and offer it to suitable patients that would benefit from it. We are hoping to accrue 30 patients, and we got our first patient a couple of weeks ago and we’ve got another couple in the works, so it’s exciting that we’re actually getting somewhere, and things are underway.”

“We’re hoping to prove that it is feasible to treat patients in either the supine or prone position on the MR Linac and we then want to use that towards some other studies that we’re looking at, because we wanted to make sure that we could treat patients with APBI safely and effectively on the MR Linac with a sort of standard treatment regime.”

“From there we can then use this knowledge to look at more novel techniques as it goes forward. So, looking at sort of some higher doses in less fractions, or higher doses in less treatments.”

How Important are Donations in Advancing Treatments and Scientific Knowledge?

“Donations are extremely important. I think we are all aware that unfortunately as much as we’d love to just be able to do research, there are costs involved. It involves time, you need equipment, you need people with specialist knowledge and skills, and nobody actually does any of this alone, so I think all of that in combination to be able to get the opportunities like this one are really important.”

“It now means that I have specific time that I can set aside to focus on working on this project. I think a lot of the other challenges in research are that people undertake things and then other work gets in the way or time gets away from you because they don’t have the time or the resources to translate what they’ve learned into some findings and then presenting and sharing that work. So having the platform and the opportunities to get in, to do the research, to actually follow it through and make sure that it happens and then share those outcomes is really important.”

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Invasive lobular carcinoma is a type of breast cancer that begins in the milk glands of the breast and has spread beyond the lobules, potentially spreading to the lymph nodes and other parts of the body.

As part of a Breast Cancer Trials Clinical Fellowship project, Dr Anna Sokolova is investigating the expression of the ROS1 protein being an important target in invasive lobular carcinoma tumors, to determine if ROS1 can predict patients that will respond best to targeted treatments.

“So, invasive lobular carcinoma is a special breast cancer subtype. It’s the second most common breast cancer subtype, and it accounts for around 10-15% of all breast cancer cases. So that is around 2,400 new breast cancer diagnoses per year in Australia.”

“Invasive lobular carcinoma is also unique in terms of its pathology and clinical behavior. And patients with invasive lobular carcinoma show worse long term prognostic outcomes compared to patients who are diagnosed with the most common breast cancer subtype.”

What are the current treatment options for this type of breast cancer?

“So, in terms of treatment, patients with invasive lobular breast cancer do not have a specific targeted treatment strategy that is unique to their clinical needs. So, patients with invasive lobular breast cancer are treated in the same way as other breast cancer patients using standard treatment protocols that include surgery, radiotherapy, and chemotherapy.”

“So, there is emerging evidence that a protein called ROS1 is an important target in invasive lobular breast cancer. And there are two recently established clinical trials in Europe that are assessing the efficacy of ROS1 targeted treatment in managing patients with invasive lobular breast cancer.”

“My clinical fellowship is investigating the expression of the ROS1 protein in these tumours and trying to determine whether ROS1 is a useful biomarker that can help to predict which patients will respond to this targeted treatment.”

What benefits do you hope will come for patients in Australia and New Zealand?

“There are two clinical trials that are currently being established in Europe and there’s potential to expand these clinical trials to Australian and New Zealand patients in the future.”

“I hope that this research will identify a clinically useful biomarker that will help to identify patients who may benefit from new targeted treatment approaches in invasive lobular breast cancer. So, there are two early clinical trials that have been established overseas looking at ROS1 targeted treatment in these patients.”

“Depending on the results of these trials, they may be offered overseas to other countries and that may include Australia and New Zealand patients.”

How important is pathology in breast cancer trials research?

“I think pathology is extremely important in breast cancer trials research. It is a multidisciplinary approach, but pathology has a lot to offer in terms of identifying biomarkers, assessing tissue samples, driving the laboratory aspect of clinical research, and giving a different perspective on clinical outcomes.”

Dr Tivya Kulasegaran is a Medical Oncologist at the University of Queensland’s Centre for Clinical Research. She is passionate about improving cancer services to rural and regional centres, and has a keen interest in lung and upper gastrointestinal malignancies.

This is the third year of the Breast Cancer Trials Clinical Fellowship Program and Dr Kulasegaran has been successful in receiving a fellowship in 2024. Her project involves establishing tools for the early detection of invasive lobular carcinoma and aims to improve clinical practice and treatments for patients.

“Breast cancer in the past decade has seen some great improvements in screening and treatment and this has been translated to an overall improvement in breast cancer survival. However, a proportion of women still undergo relapse and go on to develop metastatic disease and approximately 3,000 women die from breast cancer in Australia every year.”

“As a Medical Oncologist, I see firsthand how devastating this is for patients and their families. So, we need to be able to do better. And an area that my project is going to look at is biomarkers for invasive lobular cancer and how we can pick up on cancer early and hopefully be able to initiate therapy when the cancer is smaller and more manageable. And hopefully this translates to an improvement in survival.”

“Invasive lobular carcinoma is the second most common type of breast cancer. So, it forms in the lobules or the milk forming glands of the breast. And it counts for about 10 to 15 percent of all breast cancer subtypes. It has its own unique features, it responds to treatment differently, it tends to be more endocrine sensitive tumours and has a very distinct pattern of spread.”

“The treatment for lobular cancer is similar to all the other breast cancers. Generally, it involves surgery and endocrine treatment and sometimes we offer chemotherapy and radiation which depends on the tumour stage and the patient’s overall health status.”

What are some of the challenges in treating patients with this type of breast cancer?

“So, breast cancer is not a single uniform entity. Rather, it’s a very heterogeneous disease with distinct differences in their phenotype, their biology, and its molecular features. Invasive lobular cancer particularly has very unique features, but the treatment is the same.”

“What we offer lobular cancer treatment is the same if they had triple negative breast cancer. That generally involves chemotherapy. And the challenge we have is how do we personalize our treatment to both the patient and the tumour so that we’re able to target it and give us a better efficacy than just standard chemotherapy alone.”

“We don’t want to over treat a patient and expose them to all these toxicities that can have a significant long-term impact. At the same time, we don’t want to under treat. You want to be able to strike that fine balance. The other thing that we would love to do more in clinical practice is have targeted therapies, so therapies that’s targeted to the specific cancer.”

“I think circulating tumour DNA has the potential to be able to address this. It enables us to learn more about the tumour biology, its complex genomic landscape, and can be a very reliable predictive and prognostic biomarker. So, circulating tumour DNA, or CTDNA, is an emerging and promising biomarker. So, it refers to cancer DNA that’s being shed into the blood. And with a simple blood test or a liquid biopsy, we can pick up on these cancer cells.”

“The implications for patients is extensive. Firstly, if we can identify those cancer cells early, we can initiate therapy early. We can identify mutations which can open up a window of opportunity for targeted therapies. We can monitor treatment response. So as a patient progresses through their treatment, we can get real time monitoring or real time tracking of their response and identify if there’s new mutations coming through.”

“And we can identify and prognosticate patients. So, we can pick up on the patients that have a higher risk for relapse, and maybe these are the patients that will benefit from more intensive treatment and follow up.”

Would you say this is an exciting area of research?

“Yes. Very exciting. There’s so much potential, and it really is a valuable surrogate when assessing disease burden. It’s non-invasive or simple blood test makes it very appealing to patients, and it gives us an opportunity to look deep inside the tumour and learn from it and its genetic material.”

“We do have things that we need to tease out, for example, the validation and the standardisation of these procedures. But I’m very excited for what lies in the future. Results from this project and other similar trials should be made available in the next few years, and I think it’s very promising.”

What are your hopes for the future of this research?

“Well, I really hope that something promising comes out of this. I hope that we will identify new biomarkers and to help clinicians be able to learn more about the tumour, learn its mechanism of resistance, be able to tailor their treatment according to what they’re seeing, and to be able to either intensify or de-escalate treatment based on the biomarkers.”

“So, I hope that we’re able to move towards this era of precision oncology and that is tailoring our treatment according to the patient and their tumour.”

Dr Kylie Snook is a Breast Surgeon based in Sydney, and was a guest speaker at our 2023 Annual Scientific Meeting in Auckland, New Zealand. We spoke with her about the treatment changes that have occurred over recent years in breast reconstruction and radiotherapy.

“I’m talking on the conundrum of mixing mastectomy with the need for post-mastectomy radiotherapy breast reconstruction. This is an ever-changing area and something that when I first started practice what I was doing then is very different to what I’m doing now.”

“I’m also exploring my experience over the last 15 years and how my practice changes evolved and where we really need some really great clinical trials that we can use to inform our practice.”

“When we first started doing this, when I started practicing about 15 years ago, the standard treatment for breast cancer, including if someone needed a mastectomy and they needed radiotherapy, a lot of the time surgeons were saying ‘no, we won’t do a reconstruction, let’s not do it because you need radiotherapy and it’ll ruin your reconstruction, we will do it later’.”

“So, women weren’t being given a choice. And so very early on, our practice did a study looking at patient reported outcomes for women who had tissue expander-based reconstruction and then had radiotherapy.”

“Tissue expander reconstruction at that time was a little bit controversial when radiotherapy was needed. But what we’d shown from our study was if you give patients a choice, and they choose a tissue expander, knowing that they may not get the most perfect outcome long term, they were just as happy as the patients who had other types of reconstruction, or had no reconstruction at all.”

“So, I guess what we showed was, if patients are given a choice, that’s the best thing to do. And so, from there our techniques have changed as our practices have evolved and as surgical advances happen. And so, we’ve moved a lot of the time away from two-stage surgeries to just putting the implant straight in.”

“Rather than putting it on the muscle, we put it in front of the muscle and whilst that seems to be a good idea with radiotherapy, I’m certainly seeing negative changes much earlier on than we were doing with the older techniques. So, what I’m looking at is trying to optimize and to improve that for patients long term.”

What is Pectoral Implant Reconstruction?

“So, pre-pectoral reconstruction refers to a technique used with breast implant reconstruction as opposed to using our own tissue for reconstruction. So, if we’re using a breast implant, it refers to the position of where we put the implant. So, with pre pectoral, we put the implant in front of the muscle, as opposed to the more traditional method of doing breast reconstruction, which always used to be putting the implant or the tissue expander under the muscle, which is called sub-pectoral.”

“There is some controversial data out there from studies that are quite small. And so there are studies that suggest maybe there’s higher infection rates with pre-pectoral reconstruction. There’s also potentially higher loss of implant from infection because the infections are harder to treat.”

“But then we’ll find another small study which shows that it’s fine. So, the problem with the data out there for us as surgeons is that it is conflicting, and there’s lots of very small studies out there. But what would be ideal is to look at some really good quality randomized studies in this area.”

What is the Radiotherapy Conundrum?

“The radiotherapy conundrum refers to trying to mix in radiotherapy with breast implant reconstruction, because we all know, if you add radiotherapy to an implant-based reconstruction, the outcomes may not be as good as they would be if the patient didn’t have radiotherapy. But there’s much better quality of life outcomes.”

“In terms of complications, we know that it does have potentially worse outcomes than if a patient doesn’t have radiotherapy, but if you need it for your cancer, you have to have it. So, the conundrum is really: how do we mix in an implant-based reconstruction with the radiotherapy and try to get the best outcomes both short and long term?”

“I’d love to see us not giving radiotherapy to patients who have a complete response to chemotherapy, because the current protocols are that if we know a patient’s going to need radiotherapy before chemotherapy, we still give it anyway afterwards, even if the cancer completely goes away.”

“What I would love to see is a clinical trial in these sorts of women who need a mastectomy, looking at if the cancer completely disappears, that we can avoid radiotherapy in the future.”

Dr Cristin Print is a Professor of Pathology and Molecular Medicine in Auckland, New Zealand. Dr Print has an interest in bioinformatics in breast cancer, which involves taking large amounts of data and distilling clinically useful information from that data.

We spoke to him about the opportunities for research in this area, and how it can be used to generate better care for future patients.

“For people like me, this has become really exciting recently as we move into this precision medicine world, where for every patient who has a molecular analysis on their cancer in order to determine therapy, that’s also an opportunity for research to use that information to generate better care for future patients.”

“As we’re moving into this precision medicine world, where so many new therapies are becoming available, and a molecular analysis of a patient’s tumor helps determine whether they’re going to respond to that therapy or whether they’re just going to get toxicity and cost, then bioinformatics is playing a role clinically in helping stratify the right therapy to the right patient.”

“But it’s also playing a role with things like liquid biopsies for identifying small amounts of disease after treatment or relapse. It plays a big role in identifying whether patients are likely to respond to some of the newer immunotherapies.”

What does the future look like for bioinformatics in the breast cancer space?

“I personally think we are starting to ask more and more complex questions. When I’m analysing genomic data from a person with breast cancer, then their tumor and their inherited germline, there’s 99 percent of the information that I still don’t really know what it means.”

“So, research is really important and the idea of transdisciplinary teams with computational people, clinical people, lab people, working together to investigate increasingly complex aspects of breast cancer.”

“I think that’s the future in identifying new therapies, new diagnostics. And you know what, I think it’s actually a dual edged sword. It’s very sad that there’s so little we understand about breast cancer still, after all these years research. But that brings me hope, because that residual gap that we don’t understand, if we can find the jigsaw puzzle pieces and start to fit them into the puzzle, you imagine what we can do in future years.”

What are your hopes for the future of breast cancer research?

“One of the big things I hope in breast cancer research is that we can discover how to use immunotherapies in a broader set of patients who have breast cancer. I hope that we can discover a lot more about what we call pharmacogenomics, understanding how genes can influence how drugs work, to identify therapies that may have less side effects from individual patients.”

“I know when I talk to people with cancer, often the main thing they bring up with me is the terrible side effects they’ve had from their therapies. So, the question we have is can we do a little bit more to identify patients, side effects and therapies, and triangulate between them?”

Dr Holly Keane is a Breast Surgeon at the Peter MacCallum Cancer Centre in Melbourne, with an interest in the areas of pain management and tailored screening for breast cancer patients.

We spoke with Dr Keane about pain after breast cancer therapy, its implications in day-to-day life for breast cancer patients, and some ways to reduce pain during recovery.

“Pain, including post mastectomy pain syndrome, is something that I’ve looked into quite substantially. I’m also very interested in the screening of high-risk women and tailored screening. All of these projects I started working on within my fellowship in San Francisco and I’m trying to continue back in Melbourne, Australia.”

How common is pain after breast cancer therapy? Is it something that affects everyone?

“So, I wouldn’t say all women, but it is a majority. In the literature, the incidence of post mastectomy pain syndrome is between 25% to 60%, but I think it could be even higher than that simply because clinicians don’t always ask about it and it’s not always identified or documented.”

What are some ways that people can reduce pain after breast cancer therapy?

“So, the lifestyle interventions that we talk about include exercise and having a normal weight, but that isn’t specific to post mastectomy pain. It’s not really been shown to decrease that incidence, but it improves breast cancer specific survival, and we know that it improves outcomes during chemotherapy and other breast cancer treatments.”

“But the ways to specifically reduce pain can include oral painkillers, some neuropathic pain tablets work as well. But my interest and what I was talking about at the Breast Cancer Trials conference this year was an injection specifically into the nerve that is cut during mastectomy, that comes out of the chest wall and it forms a little neuroma, which can be targeted with local anesthetic and with the steroid injection to decrease this neuropathic pain.”

“So, simply we must get clinicians, surgeons, oncologists, radiation oncologists just to ask about the presence of these symptoms. Asking the patient what type of pain they’re experiencing, is the pain felt under light touch or are they experiencing constant pain over the mastectomy field or over the breast or reconstructed breast.”

“Once you know the answer, if the patient said yes, that they do get that sort of pain, you just simply examine the patient in the clinic room. So, they just lie down, you palpate along the inframammary fold. And if there’s what’s called a ‘trigger point’, which is when you palpate with your index finger and your thumb and the patient sort of hits the roof with pain, you know that there’s a neuroma lying underneath. From there you can simply grab a syringe with the local anesthetic and the steroid in the mix in the syringe and inject it directly into the patient. And many women will have instant results, which is very important and extremely impactful for them.”

“So, we should ask about it with everyone who’s had breast cancer surgery. Hopefully we can get the word out that this is available and is opportunity for all patients. People who treat breast cancer need to be aware of this intervention, and everyone should be able to do it including surgeons and you know other physicians as well.”

As an addition to this, how important is diet and exercise in reducing pain after breast cancer therapy?

“So, there isn’t great evidence specifically for post-mastectomy pain, but certainly to help women get through chemotherapy, endocrine therapy, and radiotherapy, exercise and diet is helpful and certainly exercise increases resistance to specific pain.”

“So, I would encourage all my patients to regularly exercise and it’s going to be moderate to high intensity exercise, three to four times a week. So, getting your heart rate up and sweating. In terms of diet, I mean we heard about diet yesterday during one of the talks. There are some links, but certainly a well-balanced diet is strongly encouraged.”

What advice would you give to a patient who was experiencing this sort of pain after their breast cancer therapy?

“Most importantly, let your specialist know, and then hopefully they will be aware of this simple intervention, and if they aren’t able to provide the intervention themselves, they can refer you to a surgical oncologist to be able to perform the injection.”

What are your hopes for the future of breast cancer research?

“That’s a good broad question. Really, my hope is in the prevention setting. You know, we do focus on this area quite a lot and have to because breast cancer is so common. There is a large focus on the treatment of early breast cancer, then the adjuvant treatments, and then unfortunately, if it gets to the metastatic stage, we need to consider all the different drug combinations and changes.”

“But we really need to be preventing this before it happens, so we don’t have to do all these highly scientific drug trials. If we can prevent more cancers from occurring, this will have a great outcome and that is why I think we should really focus a lot of our research on prevention, because we won’t need all these extra treatments if we can prevent it in the beginning.”

“We know that chemotherapy is very effective and it certainly reduces the risk of cancer returning. In women that have hormone-receptor positive early-stage breast cancer, we also give endocrine therapy. And that is very effective also in reducing the risk of the cancer returning.”

“So, if someone has a very high-risk breast cancer, they will typically get both chemotherapy and endocrine therapy. Whereas other women whose cancer is not as risky will be able to have the endocrine therapy alone without the chemotherapy.”

“One of the challenges we face in treating hormone-receptor positive breast cancer is knowing who really needs the chemotherapy. So, we need to work out who are the people that have got a high-risk of the cancer returning, and the chemotherapy is going to help reduce that risk, and who are the people that we can just give the endocrine therapy to and not have to give them chemotherapy because chemotherapy has a lot of side effects.”

“Those side effects can be quite short-term, so things like hair loss, nausea, tiredness, infections, but there are also some serious long-term side effects. So, it can cause peripheral neuropathy, there is also a small risk of heart damage and secondary cancers. So, we need better ways of really working out who are the people that really need the chemotherapy and who doesn’t.”

“And so that’s where these multigene assays have come into the picture, because they’re sort of RNA tests. They look at tumor samples predominantly in ER-positive, HER2-negative tumors. And they look at a whole lot of different genes that predict for the risk of recurrence.”

“So, there’s several of these assays and they’ve all been shown to be effective in classifying tumors into low and high-risk. And that means if you’ve got a low-risk cancer, it’s less likely to return and less likely to need chemotherapy. Whereas a high-risk cancer is the one that we really want to make sure we’re doing what we can to reduce the risk of it returning, which would mean giving it chemotherapy.”

Do these Assays differ from young women to post-menopausal women?

“So, most of the research that’s been done on these assays has been in predominantly post-menopausal women. So, a lot of the early retrospective validation studies were mainly in studies where the women were post-menopausal.”

“There have been three large prospective studies that have been completed with different assays. And in each of those studies, about one third of the women were pre-menopausal. So again, most of the women were post-menopausal.”

“There’s less data on the pre-menopausal women, but certainly when we look at the results of these prospective studies, what they showed was that you could select a group of patients who had hormone-receptor positive, HER2-negative breast cancer, and these studies were done in women who were lymph node negative or had up to three involved lymph nodes.”

“And the assays were able to look at a group who had a low genomic risk of recurrence. And overall, in each of these studies, they showed that in that group with low genomic risk, the group that, if they received endocrine therapy alone, they did just as well as if they received chemotherapy and endocrine therapy.”

“So, there was no benefit from adding chemotherapy. However, when you look at just the one-third of patients who were pre-menopausal in these studies, again, when you pulled out the patients with low or intermediate recurrence scores, the women that got chemotherapy did better.”

“So, there was a clear benefit in the chemotherapy in reducing the risk of these cancers returning. For some reason we’re seeing the post-menopausal women not getting a benefit from chemotherapy and the pre-menopausal women with the same recurrence scores getting a small benefit from chemotherapy.”

“When we look at the reason why we might be seeing this difference between the pre-menopausal and post-menopausal women and the benefit of chemotherapy, it’s very likely that the chemotherapy is causing an early menopause in the pre-menopausal women and that’s what the benefits coming from.”

“So, we’ve known for some time that giving ovarian function suppression to young women with hormone-receptor positive breast cancer, reduces their risk of the cancer returning. And so, we know in women who are close to the age of menopause when they get chemotherapy, they’re likely to go into an early menopause.”

“And in the studies in young women, where we looked at the gene expression assays, the women who were benefiting the most from chemotherapy were those over the age of 40, who were more likely to go into menopause. So, I think the next big question really is yes, there’s a benefit from chemotherapy in these women, but is it from ovarian suppression or is the chemotherapy having an effect independent of ovarian suppression?”

“Unfortunately, in the studies that have been conducted so far, we can’t answer that question because in all these trials, the endocrine therapy that was given in those young women was suboptimal. Most of it was tamoxifen only, and it was less than 20 percent of women across those studies that received ovarian function suppression.”

“So, if you’re giving maximal endocrine therapy in a young woman, which is the ovarian function suppression and aromatase inhibitor, we don’t really know if there is any benefit to chemotherapy. And that’s why we need more research to answer this question.”

What are your hopes for the future of breast cancer research?

“My hopes for the future of breast cancer research are further along this same line. I hope that we get better at firstly giving targeted therapies, and therefore have less reliance on chemotherapy, and that we become better at working out who really needs the chemotherapy. So that the people we’re giving it to we know are really benefiting from the treatment, and we’re not giving it to a whole lot of people that are not going to benefit chemotherapy and all the unwanted side effects.”

“So, I think that for the future I’m hoping we see a lot less chemotherapy use, and a lot more targeted therapies and therapies with less side effects.”