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Jul 30, 2020

In this episode, Dr. Susan Dent, a breast cancer oncologist at the Duke Cancer Institute and Co-Director of the Duke Cardio-Oncology Program, discusses how to optimize cardiovascular health in patients with cancer and survivors as well as strategies to mitigate cardiovascular toxicity during and following completion of cancer treatment.



ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Susan Dent, a medical oncologist at the Duke Cancer Institute and co-director of the Duke Cardio-Oncology Program. Dr. Dent will discuss how to optimize the cardiovascular health of patients with cancer and survivors. Her research on this topic will be presented during the ASCO20 Virtual Education Program. Dr. Dent receives grant funding from Novartis.  Full disclosures can be found on our episode pages.


Dr. Dent, welcome to the ASCO Daily News podcast.


Dr. Susan Dent: Thank you.


ASCO Daily News: Dr. Dent, there are 16 million cancer survivors in the United States. And as the survivorship population continues to grow, the association between cancer treatments and the development of serious cardiovascular complications has become more evident. Can you tell us more about this?


Dr. Susan Dent: Thank you. Yes, you're right. We are certainly seeing more survivors of cancer, which is very encouraging. However, as a consequence of that, we are now seeing more cancer survivors either develop cardiovascular disease or present with an exacerbation of preexisting cardiovascular disease. And the question is, why are we noticing that now?


I think as oncologists, we used to focus solely on the treatment of an individual's cancer and trying to cure that cancer and promote for survivorship. But what is clear now is that as individuals come to us for treatment of their cancer, they have preexisting cardiovascular risk factors. We know our population is aging. They come to us with preexisting hypertension, diabetes, or maybe even cardiovascular disease. We then treat them with cancer therapy that may exacerbate that or contribute to that. And then as they survive longer, we're seeing the cardiovascular consequences of preexisting risk factors in combination with cancer therapy that may promote the emergence of the cardiovascular disease.


So it's not as simple as just seeing a cancer patient and giving them cancer therapy anymore. We have to consider that cancer therapy in the context of the individual that we're treating and their preexisting cardiovascular risk factors to try and really prevent long-term cardiovascular disease. So while we're curing them of their cancer, we also want to try and make sure we promote good cardiovascular survivorship and cardiovascular health.


ASCO Daily News: Can you tell us about the patient populations that are presenting with more serious cardiovascular complications? Are breast cancer patients more likely to develop cardiovascular problems than patients with other cancers?


Dr. Susan Dent: That's a very good question. I think that a lot of the attention has been on the breast cancer population because we know that this is a population that's been exposed to anthracyclines in the past. We've used anthracycline sort of as a backbone of many of our therapies and then subsequently with the introduction of HER2 targeted therapies. So there was a lot of focus on this population, and that's where a lot of the research is looking at the risk of developing cardiovascular complications.


But it's not specifically the cancer per se. It is what we're treating those individuals with. So, for instance, if it's someone with renal cell carcinoma who is given tyrosine kinase inhibitor, that could lead to hypertension. And if they have preexisting hypertension, perhaps now it's exacerbated by the drug that we give them.


So the cancer is important in the context of the cancer therapy that we are offering them. And what we've learned over the last decade is that there are many cancer therapies that we offer our patients that can have cardiovascular consequences, not just on the heart. We think of the heart and heart failure. But sort of modern cancer therapies can lead to increased risk of hypertension, increased risk of arrhythmias, increased risk of prolong QTC, which is sort of a big issue right now, and in rare cases with immunotherapy, for instance, rarely myocarditis.


And so the cancer therapy that we deliver impacts the whole cardiovascular system, not just the heart, which is sort of where many of us think about heart and heart failure. So it's complex. And so we have to think about that whole individual. What are they coming into the cancer treatment with? What are their preexisting cardiovascular risk factors? What are we going to be giving them in terms of their cancer therapy, including radiation? And putting those together, what are the potential complications from that combination for that individual and their cancer?


ASCO Daily News: Right. It is very complex, indeed. So what is your recommended approach for monitoring cancer survivors and reducing their cardiovascular risk?


Dr. Susan Dent: I think it really starts at the beginning when we see these patients in our clinic and we start thinking about what we're going to offer them for cancer therapy. So survivorship really starts from the beginning when we first see these individuals. And the most important thing I think we need to think of as oncologists is thinking about what their risk factors are upfront when we're considering their cancer therapy.


So if I have someone coming into my practice, a breast cancer patient, and they have already have preexisting diabetes and hypertension, and I'm going to offer them an anthracycline and maybe HER2 targeted therapy, I need to think about optimizing those cardiovascular risk factors before, or at least as we start, the cancer therapy, because if we don't, we may get into trouble either during their cancer therapy or certainly after their cancer therapy. So it really needs to start at the beginning.


I think as oncologists, what we often do is we give our cancer therapy, and then when patients develop cardiovascular issues or problems, we then sort of refer them or ask for help from our cardiology colleagues. However, this is a very, I would say, reactive approach. We have to be more proactive in thinking about these things upfront.


You know we've now seen, for instance, with breast cancer survivorship improving, we're now seeing that those patients route seven, eight, nine years from the breast cancer diagnosis, more women are dying of cardiovascular disease than recurrence of their breast cancer. And I think as a breast cancer oncologist, that was a real eye opening study for me to see is that we're doing great in terms of the cancer survivorship, but we don't want to cure their cancer only to have them die of cardiovascular disease a couple years down the road.


ASCO Daily News: So what are the proactive steps that should be taken then so that a breast cancer patient, for example, has that attention that is required by the oncologist at the start, at the beginning of her cancer treatment if she has hypertension - addressing that issue at that point while she's getting her chemotherapy, so that she is not one of those tragic cases seven years post-treatment who has serious cardiovascular problems and potentially a fatality?


Dr. Susan Dent: That's a very good question. I think that, first of all, as oncologists, we need to be more aware or just to think about assessing patients as they come into their treatment. And I would have to say I don't think we're quite there yet. I don't think as oncologists that we're actually thinking about assessing cardiovascular risk factors when we start cancer treatments. So the first thing is to think about it.


The second thing is that we then have to start thinking about how we can look at assessing the risk factors. So there's a very sort of simple ABCDE approach to this that Dr. Michael Fradley will be speaking about in our educational session. A stands for just awareness of some of the cardiovascular risk factors. B, blood pressure monitoring, we know that hypertension is a big issue for almost half the US population. C stands for coronary artery disease screening. And D stands for diabetes control, healthy dietary choices, an E for exercise. And you'll hear more about this in our session, but just thinking about these things.


So how can we, as oncologists, even drill that down more? I can tell you what we're doing here at Duke is that we are trying to set up a screening process for all of our patients, starting out with the breast cancer population to begin with, so that we are building in our electronic health record-- we use Epic at Duke-- a screening process before patients start their treatment to try and identify those patients who might be at high risk of experiencing complications based on their history of risk factors, including, for instance, their BMI, body mass index, smoking history, diabetes, and so on.


And if those patients are deemed to be at high risk, we are trying to bring them into see a cardiologist with some interest in this area, cardio-oncologists to see if we can optimize any risk factors as they're starting their cancer treatment. I think this is the way that we have to move towards more proactive approaches, rather than waiting until these individuals run into problems with their uncontrolled hypertension or uncontrolled diabetes, because we certainly know that when they're on their cancer therapy, these things can occur. So this is a real shift I think for oncologists to try and consider of this approach. But I think it really is where we need to go.


There's also some research going on in the area of primary prevention. In other words, if there is an individual that you think might be at risk or if they're undergoing cancer therapy, that might place them at higher risk. There have been a number of studies looking at can we prevent them from developing cardiotoxicity based on cardiovascular medications that are out there?


ASCO Daily News: Well, there are a lot of interesting clinical trials underway in the cardio-oncology space right now. Can you tell us about some of these?


Dr. Susan Dent: My talk at the educational session will focus on some of the prevention trials. And most of the literature actually is on breast cancer. But there have been several trials that have looked at can we actually prevent cardiotoxicity or cardiovascular toxicity? These trials have essentially all been in the breast cancer population. They've been in patients who've been exposed to anthracyclines and in some cases HER2 targeted therapies, such as trastuzumab. And what they did is they randomized patients to receive cardio protective medications, such as an ACE inhibitor or a beta blocker or an ARB versus placebo. And they looked to see if they could prevent drops in the left ventricular ejection fraction, because as we know, this can occur with anthracyclines and HER2 targeted therapies.


Now, these studies, five of them in particular, three of those, three showed a positive benefit to giving these medications upfront versus two studies which showed no benefit. However, I have to say that how they measured benefit was as an attenuation in drop of LVF. And they were able to prevent a drop, but only in about three or four-- actually, I should say only about 3% to 4% prevention in drop. So in other words, if you had an LVF of 60%, it would prevent your ejection fraction dropping to 56%.


And so while that is encouraging, I would say, is it clinically meaningful? And so I think we need to do studies that include larger populations and populations at risk. Most of the individuals in these studies were healthy women in their mid 50s with very few cardiovascular risk factors. So moving forward, there is interest in trying to identify those patients at greater risk and then looking at the potential benefit from giving them cardiovascular medications upfront prior to starting their therapy.


ASCO Daily News: Are there any other trials that we should be keeping an eye on at the moment?


Dr. Susan Dent: There is another interesting study called UPBEAT. And what this study is it's looking at women with stage 1 to 3 breast cancer. And they are going to be looking at the cardiovascular health of these women, not only during the course of their therapy, but well into survivorship. So as women are starting the cancer therapy, they will undergo fitness testing. They will have cardiac MRI to look at their cardiovascular function. They will also be doing cognitive testing to look at the impact of cancer therapy on cognition. And these tests will reoccur throughout their treatment and then well into survivorship for several years.


And the reason why this is important is that we do not have any long-term data on the cardiovascular and cognitive effects of cancer therapy on patients. There's been a lot of literature in this space in the pediatric population where they've followed children for many years, but not in adult cancer survivors. So I'm really excited about this study. It's being done at a number of studies throughout the US. The PI is Dr. Greg Hundley. And we are certainly doing this study at Duke. And it will really provide some important insight into the long-term consequences of cancer therapy for patients.


ASCO Daily News: What role can exercise and diet modification play in improving the cardiovascular health of patients with cancer and survivors?


Dr. Susan Dent: We have always talked about exercise, but I don't think in the oncology world we've been as committed to it as we should. If you look at cardiovascular disease when individuals have a cardiovascular event, whether it be myocardial infarction or angina, they'll often be put into an exercise rehab program. We don't think about that after an individual goes through their cancer therapy. However, I think there is now clear evidence that exercise can be beneficial for our patients. In fact, it could be beneficial while they're going through their cancer therapy. And clearly, it can be beneficial into survivorship.


So the American Heart Association came out with a statement last year advocating for the benefit of exercise in our patient population. And subsequent to that, there are some ongoing studies looking at a combination of exercise and diet modification to try and deal with some of the risk factors, such as blood sugar control and hypertension. And I think all of these are actually combined when we look at overall risk. So I think that's a very exciting area is the whole field of exercise and I'll say exercise rehab for our patient population. I know at M.D. Anderson, for instance, many of their patients will be offered an exercise rehab program.


It also speaks to mental health I think as well in dealing with some of the fatigue that patients experience after they complete their cancer therapy. There's some also studies going on looking at drugs like statins, which we typically think of for the treatment of hypercholesterolemia. But certainly, these studies are looking at can statins actually benefit patients in preventing cardiovascular toxicity?


And finally, the other thing I'd like to say is that-- which we haven't touched upon-- is cardiovascular imaging. So there is research going on out there to try and determine what are the best cardiovascular cardiac imaging strategies that we can use to detect early evidence of cardiovascular toxicity. So Dr. Ana Barac is going to speak to that at our educational session. And she's going to discuss in what patients should we be using certain cardiovascular imaging techniques, such as echocardiograms, such as cardiac MRIs? When should we be using these? How should we be using these to either detect cardiovascular toxicity early? And can these techniques help us, I should say, even into survivorship? That along with cardiac biomarkers and how can they help us detect cardiotoxicity at an earlier stage?


So as you can see, there's lots going on in this space, not only from drugs that we can potentially prevent these toxicities, to exercise and lifestyle intervention, to cardiac imaging strategies, really looking at it from the very beginning prior to starting cancer therapy through their cancer therapy well into survivorship. Lots of opportunity to sort of look at different points where we can try and help individuals to really promote cardiovascular health.


ASCO Daily News: Excellent. I'd like to remind our listeners then that Dr. Dent's research on optimizing cardiovascular health in patients with cancer and survivors will be presented during the ASCO20 Virtual Education Program. And her article, "Optimizing Cardiovascular Health in Patients with Cancer, A Practical Review of Risk Assessment Monitoring and Prevention of Cancer Treatment Related Cardiovascular Toxicity," has been published in the ASCO Educational Book. Thank you, Dr. Dent for this insightful conversation today.


Dr. Susan Dent: Thank you.


ASCO Daily News: And thank you to our listeners for joining us for this episode of the ASCO Daily News podcast. Please take a moment to rate, review, and subscribe.



The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.


COI Disclosure: 

Dr. Susan Dent

Honoraria: Novartis Canada

Research Funding: Novartis US