Expert Emphasizes Exercise to Minimize Cardiac Toxicity in Breast Cancer

Susan Faye Dent, MD

Today, patients with breast cancer are living longer as a result of significant treatment advances being made; however, with that comes an increased risk of short- and long-term adverse events (AEs), said Susan Faye Dent, MD.

Cardiovascular events from novel drugs pose a particular concern, said Dent. The importance of exercise, cardiovascular risk assessment, close monitoring of high-risk patients, and collaboration between oncologist and cardiologist is now an essential component of patient care. This has resulted in the birth of a new subspecialty of medicine: Cardio-Oncology.

Cardio-Oncology is a growing and maturing field — we need to consider the health of the individual as a whole and not just their cancer," said Dent. "We have become very good at treating cancer, but we have to remember, it's not just a cancer. We are treating the entire person."

In an interview during the 2019 OncLive^® State of the Science Summit™ on Breast Cancer, Dent, medical oncologist, professor of medicine, associate director of Breast Cancer Clinical Research and co-director of the cardio-oncology program at Duke University, discussed the importance of cardiac health in patients with breast cancer.

OncLive: What are the cardiac-associated toxicities identified in breast cancer?

Dent: We've made great advances in breast cancer treatment, particularly early-stage disease, where today we can expect about 90% of women to survive at least 5 years after their diagnosis. That is good, but we need to remember that these women are also at risk of the long term side effects of their cancer treatment, including cardiovascular toxicity.

We've known for a many years that certain drugs, such as anthracyclines and HER2-targeted therapies, can affect cardiovascular health. Long-term, they can lead to a weakening of the heart, which can results in cardiomyopathy or heart failure. The last thing we want to do is cure someone of their cancer only to cause permanent heart damage. Today new and better breast cancer drugs are not only curing cancer, but they are keeping women alive longer who have metastatic or advanced breast disease. [However], these drugs can have cardiovascular side effects such as increased blood pressure, increased risk of blood clots in the leg or the lung, or arrhythmias.

Therefore, while it's great that we're making these advances in patient care, we need to pay more attention to the short and long term consequences of prescribed cancer therapies.

In one breast cancer study, women over the age of 65 years, who were about 8 years out from their breast cancer treatment were at a higher risk of dying of cardiovascular disease than of recurrent breast cancer. For oncologists ,this should be a wake-up call - it's not just breast cancer recurrence we need to think about but the entire individual.

Are anthracyclines and HER2-targeted agents the most common therapies that have been linked to cardiac toxicity?

The anthracyclines and the HER2-targeted agents are drugs that we have used extensively in in the treatment of breast cancer and for which we have the most data. As previously stated these drugs have been associated with decreases in heart function (contractility) and in some cases heart failure. This can occur acutely during cancer treatment or many years later.

There are newer breast cancer drugs, such as the CDK4/6 inhibitors, that have been associated with associated with prolongation of the QT interval which could lead to an arrhythmia . Endocrine therapy such as aromatase inihibitors can adversely affect bone mineral density and lipid (cholesterol) profiles. Capecitabine (Xeloda) which is more commonly in the treatment of advanced breast cancer, is associated with coronary vasospasm.

Immunotherapy has led to great advances in the treatment of a number of solid tumors including melanoma and lung cancer. Now patients with advanced (metastatic) triple-negative breast cancer are experiencing clinical benefit from administration of atezolizumab given in combination with nab-paclitaxel. Immunotherapy, in rare cases, can be associated with myocarditis which is difficult to diagnose and treat.

Does the impact on cardiovascular health differ dramatically between fitness levels of patients?

That's a very good question. What we do know is that if you have two individuals, one who is healthy with no cardiovascular risk factors and an older individual with two or more cardiovascular risk factors, the older individual is going to be at higher risk of experiencing a cardiovascular event.

Two years ago, ASCO came out with a guideline looking at how should we define cardiovascular risk in individuals prior to, during and following completion of their breast cancer treatment. Those guidelines give us some sense of how to determine which patients may need closer surveillance during and following their cancer treatment.

For those high-risk patients, I would advocate oncologists work closely with a cardiologist, cardio-oncologists, to try and effectively manage patients co-morbidities and risk factors, in order to prevent both short and long-term cardiovascular toxicity form their cancer treatment.

It's all about prevention now, and we are moving away from a more reactive approach—referring to a cardiologist when a patient is in trouble—to a proactive approach. How can we help that individual get through their cancer treatment, even though they have a number of underlying cardiovascular risk factors?

What additional agents are being advised to counteract this risk?

We advocate control of cardiovascular risk factors as much as possible. If you have hypertension, that needs to be under optimal control, as well as diabetes or any other cardiovascular risk factor. There are ongoing studies looking at giving cardiac-type medications upfront prior to starting cancer therapy, particularly in women who are at risk ,to try and prevent cardiovascular toxicity. It's a multi-pronged approach.

The second thing is exercise. We know that patients become deconditioned during their cancer treatment. In breast cancer, exercise has been shown to be beneficial in promoting overall health. It doesn't change anything in terms of reducing the risk of cancer recurrence, but it certainly helps to maintain the fitness level of women. We know from one clinical trial that a 50-year-old women, at the end of her breast cancer treatment, has the exercise capacity of a sedentary 70 year-old female. It is not surprising that these women complain of feeling fatigued months after completing their treatment.

Have any other guidelines committees come out or have any other initiatives launched?

There are a number of organizations such as the European Society of Cardiology, the European Society of Medical Oncology, the American Society of Clinical Oncology and the Canadian Cardiovascular Society that have produced position papers and guidelines, which clinicians can use to help guide them in identifying breast cancer patients who are at risk of experiencing cardiovascular toxicity from their cancer treatment as well as potential prevention strategies. These guidelines inform us on how we might follow these women after they have completed all of their cancer treatment.

However, a lot of these guidelines or position papers are based on expert opinion - outside of anthracyclines and HER2-targeted therapies, we don't have a lot of good, high-quality evidence. Therefore, it is important that we promote research in order to generate high-quality evidence that can lead to the production of higher-quality evidence based guidelines.

With that lack of robust data, are there any trials planned to address that?

There are trials that are investigating if giving heart medication to women upfront can prevent cardiovascular toxicity. Other studies are looking the best cardiovascular imaging strategies to detect heart damage. In certain cases, we may be over-monitoring women in terms of cardiac function while in other cases, we are under-monitoring.. There are also trials investigating the role of cardiac biomarkers (eg troponin) in predicting those women who will develop cardiac problems. We are just opening a study here at Duke that is being conducted across the United States called UPBEAT. Essentially, this and epidemiological study looking at the long-term cardiovascular consequences of cancer therapy in women undergoing treatment for early breast cancer. We will be assessing exercise capacity and cardiac function prior to starting chemotherapy, during their treatment and for several years following their treatment. By doing so, we are going to get an idea of the short and long term impact of modern breast cancer treatments on cardiovascular health. That's just one example of an epidemiological study where we're trying to gain some idea of cardiac outcomes based on the cancer treatment they had.

Was there anything else from your presentation that you would like to emphasize?

I want to emphasize the importance of oncologists and cardiologists working together as a cohesive unit. Acquiring all this knowledge is only good if oncologists are comfortable proactively referring patients to a cardiologist. We have tended to be more of a reactive specialty; when people get into trouble with her cardiovascular health we refer them to a cardiologist to try to improve things so we can continue the patients cancer therapy. We need to be assessing cardiovascular risk prior to starting women on their breast cancer treatment and referring those patients who may benefit from optimizing their cardiovascular risk factors.

And it is not just cardiologists and oncologists that are involved in the care of these cancer patients. It's pharmacists who know the side effects of old and new cancer drugs very well as well as exercise physiologists, nurses and other allied health care professionals who are a component of the health care team.