Lab-Grown ‘Hearts’ May Protect Breast Cancer Patients From Toxic Drugs

Breast cancer patients undergoing chemotherapy are typically warned that certain chemotherapy drugs can cause heart problems.

Now, new research has found a way to predict which patients may be at risk for heart issues. And, an existing medication may alleviate help some heart damage.

People with a specific type of breast cancer often end up taking a drug called trastuzumab (brand name Herceptin), which can help block cancer growth. But researchers have also found that the drug can sometimes cause dangerous cardiac side effects.

Now, researchers are using stem cells to grow tiny organoid “hearts” to figure out which patients will react badly to the medication.

Being able to identify which patients are likely to develop cardiac dysfunction induced by chemotherapy and Herceptin, could be key to successfully treating patients.

“We could use this method to find out who’s going to develop chemo-related toxicity and who’s not,” said Dr. Joseph Wu, PhD, a professor of cardiovascular medicine and radiology, and director of the Stanford Cardiovascular Institute, in a statement. Wu is one of the authors of the research, which was published in Circulation this month.

Cardiac problems for breast cancer patients

Anywhere from 15 to 20 percent of patients with HER2-positive breast cancer (where the cancer tests positive for a protein called human epidermal growth factor receptor 2) receive the chemotherapy drug Herceptin.

A side effect of the drug is cardiotoxcity which is characterized as a type of cardiac dysfunction. While the drug helps stop or slow cancer growth, it can lower the amount of blood the heart pumps while it contracts, and can also cause heart failure.

Herceptin can cause the heart not to beat properly. Specifically, it can affect the left ventricle of the heart during or shortly after therapy, Wu told Healthline.

There is no treatment for the side effects of cardiac dysfunction, though beta-blockers such as carvedilol have been shown to lower an individual’s risk for cardiac dysfunction.

Cardiac dysfunction tends to be permanent, and if untreated, can lead to progressive heart failure, Dr. Michael Miller, a professor and director at the Center for Preventive Cardiology at the University of Maryland School of Medicine, explained to Healthline how toxicity that hurts the heart can be dangerous.

“The chemo-induced toxicity may also result in sudden cardiac death,” he added.

While some cardiotoxic complications are usually reversible upon stopping Herceptin therapy, other types of cardiotoxicity are irreversible, acute, and chronic.

Miller said that cardiotoxicity is most likely to occur with high cumulative doses of some medications.

The National Comprehensive Cancer Network reports that cardiac toxicity can be prevented by giving less of the cancer drug, receiving lower doses more often, or using a less-toxic drug.

Using lab-grown “hearts” to help patients

The reason some people experience cardiotoxicity is likely a result of a genetic predisposition, though environmental factors may contribute. Older age, obesity, and hypertension are some baseline risk factors for cardiotoxicity.

Symptoms of resulting cardiac dysfunction due to cardiotoxicity include shortness of breath, fatigue, and fluid buildup in the legs. Being able to figure out who is at risk for cardiotoxicity could mean saving some patient’s lives.

In the new study, researchers derived stem cells from the white blood cells of three healthy participants and seven participants with breast cancer. Five of the people with breast cancer had experienced cardiac dysfunction after taking Herceptin.

The researchers manipulated the stem cells to develop into heart cells, which are also known as cardiomyocytes.

When the researchers applied Herceptin to the cells from breast cancer patients who had heart dysfunction, the cells contracted less vigorously. Upon applying it to cells from breast cancer patients who didn’t have side effects, there was little change.

How a diabetes drug may help breast cancer patients

There may be a way to help combat these cardiac side effects.

When the researchers applied a type of drug called an AMPK activator, to the weakened cells, the cells consumed more glucose and contracted more vigorously. AMPK activators include the common type 2 diabetes drug metformin.

Upon treatment, AMPK activators prevented Herceptin from weakening heart contractions by increasing energy production.

Wu said they used these drugs because they could help stop the cardiotoxicity effects of Herceptin.

“They can reverse the underlying cellular and molecular changes without harming the heart,” or disturbing associated cancer therapies Wu said.

A large clinical trial would be needed to verify these findings. Now the researchers want to conduct another experiment on breast cancer patients who received Herceptin, and who were also taking metformin for diabetes.

“We need further studies validating our findings, using human clinical trials to apply the findings to routine patient care,” Wu said. The potential benefits from the extended use of the drugs should be assessed carefully in future studies, he added.

AMPK activators may also make tumor cells sensitive to chemotherapy in different types of cancers, Wu said, but more study is needed.