Ana Barac, MD, PhD, Cardio Oncologist at MedStar Heart & Vascular Institute talks about HER2 positive breast cancer and how treatment may effect the heart.
Interview conducted by Ivanhoe Broadcast News in May 2019.
I know your background is in cardiology, but for our viewers who are not familiar when you say her2 positive breast cancer, what is that?
BARAC: About 20 to 25 percent of patients who have breast cancer have one specific receptor that’s amplified on their cancers, and they respond extremely well to so-called targeted therapy. It means that therapy is designed to target that receptor and specifically target tumor cells. They are called her 2 positive breast cancers, and they respond to her2 therapies which are usually combined with other standard chemotherapies as well.
What have you as a cardiologist and your colleagues found as some of the side effects or the impacts of those drugs that are so very necessary to fight the cancer?
BARAC: These drugs have been, in the case of breast cancer, really revolutionary. This used to be one of the worst subtypes of breast cancer and now since the invention of these drugs and they started around early 2000 – that prognosis of that subtype of breast cancer has impressively improved. For women who are diagnosed with early stage, the cure percentage tends to be much higher, meaning that they are free of recurrence. And for patients with metastatic breast cancer, they live much longer. So it has really truly revolutionized the approach to breast cancer. We’ve learned early on in early 2000s that while her two targeted therapies are well tolerated in general, there are no usual severe side effects. However we learned that they can in rare instances cause heart failure. In early studies, that was actually rather common. Almost one in five patients would develop symptoms. And then some important changes were made to how medications are given, and they are given only to patients with normal heart function. So there is mandatory monitoring of heart function when these medications are given. So patients have typically an ultrasound or they can have a different test to assess heart function. We typically talk of a left ventricular heart function and we assess that in percentages. And that tells us that it’s safe to give the medication. So with those precautions, the therapy has become rather safe. And also for the first time we are able to see something that we call asymptomatic heart dysfunction. That means, for example, a patient or woman is feeling completely fine, is getting her treatment and gets an echocardiogram. And then she might get a phone call tomorrow and say hey your heart function is not great. That doesn’t mean that she is in heart failure. It just means that one number that we are following what’s called left ventricular injection fraction might have decreased slightly. It doesn’t mean that the heart is effectively pumping less. However we know that that could be a marker of a future risk of a true heart failure. So about, depending on the combination of the drugs, anywhere between 10 and 15 percent of women who are being treated with her2 targeted therapy can develop this decrease in heart function – mostly asymptomatic while the risk of true heart failure, meaning being short of breath, having leg swelling, having to come to the hospital for true heart failure, is much less. You’re talking about one to two percent during treatment.
You had mentioned the fact that there’s mandatory monitoring once women are on these drugs. Could you tell me a little bit about the clinical trial? What were you and your colleagues looking to determine?
BARAC: Yes. Our trial was called Safe heart trial. It was designed to test the hypothesis that it might be safe to either start or continue her2 targeted therapies in patients who do not have normal heart function. As I mentioned, monitoring is recommended by the FDA. It’s part of the package insert. It’s part of the standard guidelines. We know that the patients are the safest if we give them medication when the heart is normal. However we are now about 15 years or 19 years since the first approval of the medication and we know that it really has tremendous impact on the prognosis of breast cancer. So we learned about the benefit, and also over time we know that with these precautions we know that it became rather safe for the heart. So now we are left with a group of patients whose heart is not completely normal and we are asking, well, can we safely give the medication? Heart failure and cardiology world has also advanced. We have a number of medications in with which we can usually protect the heart to put it in that way. We are extrapolating from heart failure literature and say, well, if the beta blocker is good for patients with a weak heart, why don’t we try it here? So we hypothesized that if we take the patients whose heart function is not normal, they have her positive breast cancer, they need this therapy, we put them on a trial and we give them heart medications beta blocker and ace inhibitor – guideline plus one recommended medications for heart failure, can we prevent further worsening of their heart function and at the same time complete the treatment for breast cancer?
What did you find?
BARAC: It was a study that lasted for years. It was a truly collaborative effort. So cardiologists and oncologists – we had a true partnership. And I have to say that the most important leg of the trial were the patients. It was one of the most rewarding trials that I’ve ever done. Patients felt that they wanted to be in the study. There was no randomization. Everybody included in this study, our hypothesis was that they would be able to complete the trial, and out of the 30 patients included, we enrolled patients from MedStar Washington Hospital Center, MedStar Georgetown University Hospital with Lombardi Cancer Center, and also we had a collaboration with Memorial Sloan Kettering Comprehensive Cancer Center in New York. We enrolled 30 patients. Of 30 patients who enrolled, 27 successfully completed the study. So 27 women who would have not otherwise been able to receive cancer treatment have received it. We had three patients develop heart problems. Nobody died of heart issues. Patients who developed symptomatic heart failure recovered afterwards, but they were taken off the file and in those three we could not complete planned oncology therapy.
What are the implications? You had mentioned these women were so grateful. When you’re finding ways to use these drugs, what are the implications of the study?
BARAC: I think it has implications that are broader than its own findings. I think it points to the importance of collaborative care. I think that we had a privilege of chairing a group within the American College of Cardiology that is really working on advancing the awareness and training, education and clinical trials in what we call cardio oncology. Its cardiovascular care of oncology patients. And I think for that group it really emphasizing that we have a collaborative approach to treatment of patients. You cannot say well, you treat the cancer and we’ll deal with the heart afterwards. It might be late or other way around. Let’s take care of the heart and then we’ll treat the cancer later. In order to do that, you do need to have very high level of awareness, of knowledge, of trials that have to be happening at the same time. And I think that the one who is really driving the field are the patients because they are the ones who are feeling it the most. We are specialists. But there is only one patient. So with that, I think that the study was one of the studies that demonstrated that we can do it when we push and put our efforts together.
Tell me a little bit about Nancy.
BARAC: Nancy is one of the first patients on the trial. She actually came to our system because of the trial. I remember first meeting her. Now this is seven years ago, I think. She had metastatic breast cancer so it was spread. I’m not sure that we knew that her prognosis was so great, but she was already on a number of years on her2 targeted therapies and we knew that her cancer responded to this. At that time, she already had one event when her heart function went down. And there was a need to stop the treatment. And we said, well, would you be interested in participating in a trial? One impressive thing about Nancy is that she is a fighter. She is very positive energy. She said when she first met me and said I have no doubt we are going to get this right. With her first treatment, when she met us, she actually had a lot of side effects – not of her2 targeted therapy. She had to receive also standard chemotherapy, ended up in the hospital as it always happened. But she really had the spirit of let’s do this together. She successfully completed the trial. She stayed on two heart medications. And after completing the trial, her heart function always never returned to normal. It’s always her number is always under normal. I don’t think if you see her you would never say that she has heart dysfunction. She exercises. She works full time. She’s written books. She is an advocate. She’s maintaining her full functional status, including aerobic capacity. But one needs to be on the lookout. I do see her and she continues to her see her oncologist. Her heart function is always at the risk of going down, but we believe that we can truly manage it in the long run.
Is there anything I didn’t ask you that you would want people to know?
BARAC: Yes. For this population, I think there is increasing awareness. It’s not only her2 targeted drugs. I think American Heart Association has published last year a statement that I had a privilege to participate in about the intersection between cardiovascular disease and breast cancer. And I think when we medical professionals – we say oh let’s focus on breast cancer, let’s focus on heart attacks – again, they might happen in the same patient. I think there is a lot of new knowledge about the common risk factors between cancer and cardiovascular disease. A number of different treatments can affect cardiovascular health. So I think the awareness of it and the proactive approach because cardiovascular disease is the second leading cause of death in women with breast cancer, and some sometimes can even compete with that. So I think it’s a missed opportunity if we don’t as a system, as a health care system, don’t put our efforts together and try to provide the best care for these patients.
END OF INTERVIEW
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