Posted on Oct 06, 2022

After getting treated for breast cancer, many survivors are left with a higher risk of developing diseases that affect the heart or blood vessels (cardiovascular disease). Now, a new study has found that having a cardiovascular event, like a heart attack or stroke, may in turn make breast cancer grow faster.

Some breast cancer treatments can affect the heart, making survivors more likely to develop cardiovascular disease. Lifestyle changes during and after treatment, like exercising less, can make that risk even greater.

“But no one had asked the reciprocal question: If [breast cancer survivors] have a cardiovascular event, does it impact their cancer?” said the study’s leader, Kathryn Moore, Ph.D., of New York University's Grossman School of Medicine.

The answer, Dr. Moore and her colleagues found, appears to be yes. In their analysis, breast cancer survivors who had a cardiovascular event were more likely to have their cancer come back. They were also more likely to die from breast cancer.

In studies of mice, the researchers found that a heart attack leads to changes in the immune system that permit cancer to grow and spread more easily. The findings were reported July 13 in Nature Medicine.

This study presents a “new way of thinking about how cancer and cardiovascular health may interact,” said Susan Dent, M.D., an oncologist who wasn’t involved in the study. Dr. Dent is co-director of Duke University’s cardio-oncology program, which focuses on the intersection of heart disease and cancer.

Although the findings are alarming, there are things breast cancer survivors can do to lower their risk of cardiovascular disease, Dr. Moore emphasized. That includes exercising, eating a healthy diet, and controlling their cholesterol and blood pressure, she said.

These strategies may not only reduce the risk of cardiovascular disease but also improve cancer outcomes, the researchers wrote. One of the researchers is studying mice to see if exercise can prevent breast cancer from growing back after a heart attack.

Cardiac Events Spur Cancer Growth

To see how cardiovascular disease impacts cancer, the scientists first analyzed data from two older studies of women with breast cancer.

The studies tracked more than 1,700 women for an average of 12 years, during which time some developed cardiovascular disease. The team focused their analysis on those women who didn’t have cardiovascular disease at the time that they were diagnosed with breast cancer.

Survivors who developed specific cardiovascular diseases and events—namely heart attack, stroke, heart failure, coronary artery disease, or arrhythmia—had a 59% higher risk of breast cancer coming back (recurring), the researchers found. These women also had a 60% higher risk of dying from breast cancer than women who did not develop cardiovascular disease.

The team is interested in learning whether cardiovascular events are linked to similar outcomes for survivors of other types of cancer, Dr. Moore noted.

The researchers also studied mice with breast cancer. In some mice, they performed a surgical procedure to cause a heart attack. In another group of mice, they did the surgery without causing a heart attack (a “sham” surgery).

Breast cancer grew and spread faster in mice that had a heart attack. Seventeen days after surgery, breast tumors in these mice were twice as big as those in mice that had the sham surgery. Mice that experienced a heart attack also had twice as much breast cancer that had spread (metastasized) to the lungs. The scientists observed these effects in mice that were engineered to develop breast cancer as well as in mice that were implanted with mouse breast cancer cells.

Immune Cells Change After Heart Attack

Dr. Moore’s team had never studied cancer before. Their usual focus is on clogged arteries (also called atherosclerosis), which can lead to a heart attack, stroke, and heart disease. In particular, they study why the immune system goes into overdrive when arteries are clogged.

The immune system’s exaggerated response to clogged arteries can make the clogs even worse. Likewise, the immune response to cancer can sometimes make the cancer grow and spread more easily. Because of the immune system’s role in both atherosclerosis and cancer, the researchers suspected that changes in the immune system might explain why cancer grows faster after a heart attack.

The numbers of certain types of immune cells inside breast tumors differed between mice that had a heart attack and those that didn’t, the scientists found.

For instance, tumors of mice that had a heart attack contained fewer cancer-fighting immune cells and more “suppressor” immune cells—those that prevent the immune system from attacking cancer. By toning down the immune response against cancer, suppressor immune cells can help tumors grow.

Specific suppressor immune cells called monocytes appeared to be responsible for the faster cancer growth after a heart attack, the researchers reported. In mice that lacked monocytes, breast tumors didn’t grow as much after a heart attack as in mice that had monocytes.

A Lasting Impact on Monocytes

Recent studies have shown that certain diseases and conditions can lead to lasting changes in immune cells. These changes, called epigenetic alterations, affect genes without changing their DNA sequence.

In mice that had a heart attack, monocytes had widespread epigenetic changes, the team found. The changes shifted the cells’ activity from cancer fighters to immune suppressors.

The researchers also found evidence that the epigenetic changes might occur a step earlier, in monocyte precursor cells. These cells, which are stored in the bone marrow, develop into mature monocytes.

The team collected bone marrow from mice 20 days after they had either the heart attack or sham surgery. They then transplanted the bone marrow into healthy mice. After recovering from the transplant, the healthy mice were implanted with mouse breast cancer cells. More than three weeks later, breast tumors were larger in mice transplanted with bone marrow from mice that had suffered a heart attack.

This finding hints that precursors in the bone marrow may be reprogrammed to be immune suppressors, Dr. Moore explained. It’s possible that monocytes that developed from the transplanted bone marrow accelerated tumor growth, she added.

And because the experiment spanned several months, it also suggests that the epigenetic changes caused by a heart attack last for a relatively long time, Dr. Moore said.

A Message for Breast Cancer Doctors and Patients

This study highlights the need for both breast cancer survivors and their doctors to pay more attention to cardiovascular health, Dr. Dent said.

Many women who are diagnosed with breast cancer also have other diseases that raise the risk of cardiovascular disease, namely diabetes, obesity, and high blood pressure.

Those cardiovascular risk factors are not always under control when women start cancer treatment, Dr. Dent explained. “Then we give them cancer therapy, which may add to that risk. They finish their cancer therapy, and then they are sent back to their primary care doctor with little attention to their cardiovascular risks,” she said.

For breast cancer survivors, doctors should not only highlight ways to stay healthy in terms of their cancer—such as getting monitored for cancer recurrence—but also stress the importance of being heart healthy, Dr. Dent added.

Most of that responsibility rests with cancer doctors (oncologists), heart doctors (cardiologists), and primary care doctors, she said. But patients need to be aware of their risks too, she added.

“You need to be your own advocate as well.”

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