Cardiologists are not telling women with breast cancer to decline treatment — far from it. But in its first-ever statement on the most common female cancer, the American Heart Association warned on Thursday that breast cancer survivors, especially those treated with common chemotherapies, are at increased risk for heart failure and other cardiovascular diseases. And it called on cancer doctors to weigh the benefits of those treatments against the heart risks they pose.
It has been known for years that some breast cancer drugs (including some also used for other cancers) can weaken the heart muscle, causing heart failure. But the group of heart doctors is concerned that if heart symptoms arise years after cancer treatment, the link to chemo may be missed.
An older class of drugs called anthracyclines, which includes doxorubicin, can kill cardiomyocytes, which make up the heart muscle, especially in older women or those with pre-existing heart disease. Taxanes, such as paclitaxel, can cause an abnormally slow heart rhythm, while hormone drugs such as tamoxifen can cause potentially fatal thromboembolisms, or blood clots. The aromatase inhibitor anastrozole has been linked to heart attacks and other cardiovascular events. Trastuzumab (Herceptin) can cause heart failure, especially in women over 50 and those with underlying heart disease or hypertension.
In most cases, however, the absolute risk is fairly low, said Dr. Laxmi Mehta, director of the Women’s Cardiovascular Health Program at Ohio State University and lead author of the AHA’s statement, which was published in the journal Circulation. Herceptin studies have found a heart failure incidence of up to 4 percent, for instance.
The greatest risk is from doxorubicin, and it increases with the number of treatment cycles. Eight treatments at the typical intravenous dose brings a 5 percent risk of heart failure, but a 26 percent risk after 11 such treatments and a 48 percent risk after 14.
“The intent of the paper is certainly not to say don’t treat breast cancer,” Mehta said. “We want patients to undergo the best treatments available. But we also want patients and their doctors to be aware” that breast cancer drugs can damage the heart.
That’s especially important many years after treatment. Insurers usually won’t pay for cancer survivors to keep seeing an oncologist, so primary care physicians need to be aware that women who were treated for breast cancer are at higher risk of heart disease, said Dr. Otis Brawley, chief medical officer of the American Cancer Association. And if a woman goes to an emergency rooom with symptoms of heart failure, he said, triage nurses need to factor in past breast cancer treatment when making the initial determination of whether she has heart failure.
Knowing a woman’s history of breast cancer treatment can be crucial when treating her heart. Dr. Susan Gilchrist, a cardiologist at MD Anderson Cancer Center who runs the only U.S. program for women’s heart health after cancer, said she would treat hypertension, obesity, and other risk factors even more aggressively in a patient who had received doxorubicin, for instance. And awareness of how chemo affects the heart can in some cases limit the risk: giving IV therapy slowly seems to cause less risk of eventual heart failure than giving it all at once.
The AHA statement might help explain two puzzles about cancer treatment. One is why patient survival is higher at comprehensive cancer centers than in community practices, meaning those not affiliated with an academic institution. Doctors at the former are generally more experienced, and having cardiologists under the same roof can mean better management of the cardiovascular harms from cancer treatment.
“I think the general oncologist absolutely knows the side effects of cardiotoxic drugs such as anthracyclines and Her2 targeted therapies,” said Dr. Neelima Denduluri, a breast oncologist in Virginia who was not involved in the AHA statement. But primary care physicians might not be as knowledgeable, and it’s useful to “remind the busy general practitioner and the medical oncologist that they need to pull the cardiologist in.”
Another puzzle is why screening mammography, meant to detect breast cancer when it is supposedly more treatable, doesn’t seem to reduce the risk of premature death from all causes, rather than breast cancer only. In one of the world’s longest-running mammography studies, researchers in Canada found that among women aged 40 to 59 who were randomly assigned to regular mammograms, mortality after 5, 10, and 15 years was indistinguishable from women not getting regular mammograms. But beginning at 20 years, deaths from all causes were slightly higher in the mammogram group.
It may be that lives saved from breast cancer are being lost to heart disease. “Treatment-related mortality [from heart disease] is not reliably captured in breast-cancer mortality,” said Dr. H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice.
Cardiovascular disease kills more women than breast cancer. Among older women, it even kills more who have been diagnosed with localized (not advanced) breast cancer: The long-running Women’s Health Initiative reported last year that among women in their 70s with localized breast cancer, over a 10-year period 17 percent died from breast cancer and 22 percent from cardiovascular disease.