Case 3: Cardiac Risk Stratification
Dr. Kelly McCann:
Welcome to The ASCO Post Roundtable Series on Managing Cardiovascular Risk in Metastatic Breast Cancer: Clinical Insights on CDK4/6 Inhibitors. I'm Dr. Kelly McCann. I'm a breast medical oncologist and Assistant Professor at UCLA. Joining me today are two of my colleagues.
Dr. Hope Rugo:
I'm Hope Rugo, a breast medical oncologist and Director of the Women's Cancers Program and Division Chief of Breast Medical Oncology at the City of Hope Comprehensive Cancer Center.
Dr. Avirup Guha:
Hi, everyone, I'm Avi Guha. I'm an Assistant Professor of Medicine and Director of Cardio-Oncology at the Georgia Cancer Center at Augusta University, Augusta, Georgia.
Dr. Kelly McCann:
Thank you to both of you for joining me. Today we will be discussing the role that cardiovascular risk factors play in the management of metastatic breast cancer, using 3 patient case studies. Our third and final installment will focus on the importance of cardiac risk stratification.
K.G. is a 76-year-old woman who presents to the emergency department with chest pain, severe mid-thoracic back pain and dyspnea. She can deal with the pain, but she's concerned that she's so short of breath, taking her elderly dachshund, Hotdog, outside of her apartment to toilet on the grass in the immediate vicinity. Hotdog has no interest in taking a walk. She's worried about how she's going to take care of him if she can't breathe. On further questioning, she's had progressive mid-thoracic back pain for over a year and has been homebound for about 5 months. Her past medical history is unknown.
She's avoided doctors for the past 30 years after a traumatic experience with her mother's death in the ICU and she doesn't want to be told to stop smoking or lose weight. So she has avoided doctors. Her surgical history includes two C-sections and her social history includes smoking one pack per day since age 16. On physical exam, her blood pressure is 165/100, her oxygenation is 86% on room air, her BMI is 31. Breast exam is not performed due to emergency triage. Decreased breath sounds are noted posteriorly in the right lower lung and 1+ pitting edema is noted of the bilateral lower extremities. On labs, her white blood cell count is 12, hemoglobin 16, creatinine 1.3, and her troponin is slightly above the normal reference range. Her BNP is 360. Her ECG shows a normal sinus rhythm without ST elevations or T-wave inversions. Cardiology is not consulted and ECG is not formally reviewed on the day of admission.
Chest x-ray shows a large right pleural effusion. MRI of the thoracic spine shows compression fracture at T12 and there is concern for lytic vertebral metastasis. She's admitted to the hospital for a troponin rule out, thoracentesis, and additional workup. The following day, a 1.5-liter thoracentesis is performed by interventional pulmonology, but our oxygenation status only improves to 93% O2 saturation on room air. On more comprehensive physical exam after admission, K.G.'s left breast is moderately contracted with nipple inversion and periareolar purple skin discoloration. She attributes this to an injury from her 3-year-old grandson accidentally kicking her in the chest over a year ago when his mother handed him to her.
CT chest/abdomen/pelvis shows lytic bone metastases, pleural, and lung metastases. The cytology of pleural fluid is positive for ER-positive, HER2-negative adenocarcinoma. She started on letrozole, which is on the hospital formulary. CDK4/6 inhibitors are not on the hospital formulary for financial reasons. During admission and work-up, she progressively becomes orthopneic with an O2 saturation below 92% and undergoes a second 1.5-liter therapeutic thoracentesis. Two hours after thoracentesis, telemetry alerts the nursing station and covering physician that her heart rate is 170 beats/minute. ECG shows atrial fibrillation with RVR. Cardiology is consulted.
So in this patient with metastatic breast cancer and several cardiovascular red flags, what would be the work-up recommended by cardiology at this point?
Dr. Avirup Guha:
Excellent case and I believe this is probably a real case you've probably dealt with, Kelly, as well. So this is a simple AFib-RVR consult as I would start with, where I would do all the right things and don't think too much about the cancer first, because obviously you have that information, but keep it aside. So, you just go assess heart failure signs, arrhythmia symptoms, ask how they've been feeling, because a lot of this might be related to things which might be going on for a while, which she, as you said, hasn't wanted to see a doctor. And then obviously keep in mind that she doesn't want to really see you because she doesn't want to see a doctor. So to keep that in mind and act, and this is what I do all the time, I tell them that, "Hey, I am going to just treat you like you're my sister or mother or my grandmother," based on the age, "and I'm just going to sort of give you advice as I would give them."
And sometimes my grandmother doesn't listen to me, so I just tell her that, "You might choose not to listen to me, but just hear me out." So that way build some, what I call quick rapport, because you need that to have them listen to you at all. And then once I'm done with that and get some labs, BNP, troponin, which we've already done, and then CBC+CMP as a part of standard panel. Mag+TSH is important for all AFib workup. Formal cardiology read of the EKG is important. So I could tell from a distance that's an AFib EKG. Eventually you try to get a slower EKG to measure the QTc and then also an echocardiogram to look at the LV/RV functions, the valve status, if she has any pulmonary hypertension, but she has some because of her effusion. And then monitor though to assess for pulmonary embolism and now bringing in the cancer.
Cancer is a prothrombotic state, so go back there and look for PE. And sure, this patient now who has cancer is likely going to be on some medicine which might affect her cardiovascular disease, which we still don't know what is adversely as an outpatient. So have a plan to see her as an outpatient.
Dr. Kelly McCann:
And then when she is an outpatient, how soon do you think that she should be seen and what other things would you recommend at that point?
Dr. Avirup Guha:
So, it depends on what we find after I've done those initial workups. So for example, if I find an EF of 30%, 20%, and then she'll likely undergo left and right heart catheterization at that point, likely inpatient, given the troponin elevation. Assuming all that's normal and volume state is restored back to normal, she feels fine with fluid taken inside her chest and also from her chest and lungs, I would see her about 7 days with a nurse practitioner clinic to ensure that volume status remains normal, formally see her in 2-4 weeks. And when I see her in the clinic again, just ABCDE, you just harp it on and on and on that awareness of what these medicines you're going to now experience and you have to take them.
And then I always try to have a family member come along just so that they are ones they're likely going to listen to a lot more than you. When they have coronary disease, I tell them, "If your house is on fire, you have to run out of your house with one thing, which is your Plavix, and if you have anything, any valuable, that's the most valuable thing you have to run out with." So things like that where you can get them engaged in some way and then you have to decide whether you're going to do the manage or rate manage. Now we are talking about CDK4/6 inhibitors, so we are likely going to rate manage because rate management is going to prolong QTc, which is not a good thing in this situation, and then a monitor for recurrence of effusion and progression of heart failure by subsequent clinical monitoring.
I would imagine, like you said, the previous patient, now this patient I think we will likely see every 4-6 weeks initially till we can prolong up to 3 months, which is the most I would prolong. And also keep in mind, at least here, a lot of our patients are not coming from close by, so have a plan to have some form of virtual check-ins with them. And then I guide oncology colleagues, if they ask me, to a more cardiac safer regimen if it's possible. Now she might've backed herself into a corner of having a standard regimen, which she needs, but if possible, if there are choices, which an oncologist would ask me, say I will pick between A B, and C, then we'll maybe pick C, because of 1, 2, 3 ease and whatever it is. So those would be sort of the outpatient plans.
Dr. Kelly McCann:
Hope, what kind of CDK4/6 inhibitor would you prescribe in this setting?
Dr. Hope Rugo:
This is a really complicated patient, and I think there’re a number of different issues to be considering. She has lytic bone metastasis. I think all of us would be trying to figure out whether she has one area of particular increased pain or it puts her at risk, because sclerotic bone metastasis, where dense, in general it takes a lot to fracture those, but lytic bone metastasis are a little bit different. So you'd really want to get plain films for the areas of lytic disease that are weight-bearing to really make sure, because then that situation, if they're at risk for fracture, we usually radiate them. But I don't like to just radiate all the bony areas 'cause we don't want to mess up her bone marrow, or her bones for that matter, in the long-term. But that would be one thing that I would be interested in doing.
If she has spine disease, I usually get an MRI just to get a baseline evaluation. She has that big effusion and I wonder, I've seen situations where people had all these medical problems, and they have AFib when they have a lot of effusion and they're really short of breath. But when you correct all those things, the AFib goes away, because I think that maybe we don't have all the details here, but maybe there's fluid around the pericardium, etc., also irritating the heart. But in this situation, depending on how quickly she needed to be drained, she had 1.5 liters drained and then she needs to be drained again I think, right? She gets drained 1.5 liters, right?
Dr. Kelly McCann:
And it's a stress on her system.
Dr. Hope Rugo:
Yes. So the thing is, I don't like to put in PleurX catheters if you can avoid it, but I think in this situation, she's in the hospital, so if she re-accumulates quickly, even though I think that her treatment will work very quickly, I would think about a PleurX just because even if you keep it in for a month, it's probably better than tapping continuously. But otherwise, if she didn't re-accumulate, you could always hope that the treatment would kick in fairly quickly. So when she leaves, you want her to start on the CDK4/6 inhibitor. And again, I think that this is complicated. She hasn't gotten any medical care, she's a big smoker, she's hypoxic. You're all in a difficult situation here.
And as cardiac issues, I think it's a little bit of a toss-up. You don't have a specific agent, you don't want her to have a lot of diarrhea, because she wouldn't tolerate it. So, you could start abemaciclib at a low dose, but I would start at 50 twice a day. I think I'd be very comfortable putting her on palbociclib, starting at 100 mg a day, and probably what I would choose first. And I'd be worried a little bit about ribociclib just because of her cardiac issues. And also, I suspect she might have so-called hepatic steatosis or whatever its current name is now, metabolic liver dysfunction, which I think might put you at slightly higher risk. We don't know that for sure. Ribociclib liver enzyme elevation. It is tough regardless, but with a patient like this who's older, has lots of medical problems, usually we'll put them on palbociclib. How about you, Kelly? What would you give her?
Dr. Kelly McCann:
I think that's totally reasonable and there's more data coming out of, looking at some of the subsets of patients in the clinical trials like PALOMA and then even intentionally studying these patients or enrolling in clinical trials because this is a big swath of the patients that we treat. They have cardiovascular risks and they have metastatic disease and the interplay between those two things, setting her on a letrozole or an aromatase inhibitor, she's going to have an increase in her lipids potentially. She now has a thrombotic risk, not only because she's not moving around because she's not breathing, but also because of the medications that we put her on. So I think this is kind of the perfect patient to have a cardio-oncologist involved. What do you think, Avi?
Dr. Avirup Guha:
Yes, I mean, I think obviously taking care of her is going to be medically relatively easy. What I tell in situations like these when they have not seen doctors or reasons, is kind of determine things outside of medical care which might be bothering them to see us. So when I see patients in clinic, I have them fill a social determinants of health questionnaire. I know some places might be delegated to a social worker doing it, but I do it just because when I'm even picking medications, I have often choices which are less expensive medications for taking care of heart failure patients. And I also, if I see a red flag in there, things which they don't want to talk to you about because they feel like the doctor or somebody whom I don't know is going to judge me is something which you catch on and try to see if you can help them with.
And coming from a doctor when you try to help them with situations where they really don't want to talk about might be a way to get the buy-in. So if you're able to address the five different social determinants of health, which we generally deal with, one of them being access to high quality care, which would be cardio-oncology, is if you mitigate those, you're likely going to make a lot more difference than the small choices of medications. And I call it small choices, although we are discussing the choices of medications, because those are the reasons why some of these patients don't do well. And we sometimes call it noncompliance, sometimes call it difficult patient, but it's things which we never figured out because they're not sort of standard medicine textbook stuff. So I do rarely think about those in research obviously, and also in clinical care because of the population I take care of, especially from rural Georgia. So obviously cardio-oncology plus those factors. So one of the MDT, multidisciplinary care person, who is very important here is a social worker as well.
Dr. Hope Rugo:
That's a really good point, Avi, because I think social work is a critical component of how we manage patients in the metastatic setting overall as well as early-stage disease. But this patient really needs support. She hasn't ever been in the medical system before and our social workers are just a critical component that we need to all be working to continue to support because we need that for these patients. And I've had situations where patients’ insurance, probably not for this patient, but is primarily Medicare, and their share of costs for the CDK4/6 inhibitors is huge. And I think, Kelly, you and I have talked about that before and our social workers have been amazing about finding the loopholes and really the compassionate use programs, if you have a lower income, for getting these drugs. So this is really an important part of our multidisciplinary team management.
Dr. Kelly McCann:
Absolutely. So now to go to the key clinical takeaways. Cardiovascular risk assessment is an essential part in the care of women with ER-positive, HER2-negative breast cancer. The prognosis of a cancer with metastatic ER-positive, HER2-negative breast cancer is typically measured in many years. Diagnosis entails initiation of treatment for a chronic disease, not funeral planning most likely. Most patients diagnosed with breast cancer in the US are cured, but many sustain cardiovascular risks due to their breast cancer treatments. Breast cancer patients, whether they're in the curative or the metastatic breast cancer setting, should be advised to also optimize cardiovascular risk factors for quality and quantity of life. This brings us to the end of this case. Please see the other segments for further discussion about the latest research in breast cancer or visit ascopost.com.
