Chemotherapy boosts heart disease risk

By LAURAN NEERGAARD, AP Medical WriterMon Oct 8, 3:52 PM ET
Breast cancer survivors may face increased risk of heart disease — and doctors are debating if it's time to largely abandon a chemotherapy mainstay that is one reason for the problem.
Drugs called anthracyclines are a breast chemo staple despite a well-known risk: They weaken some women's hearts. What's new is research suggesting the drugs work no better than safer alternatives for most women.
It's a controversy born of success: Treatment advances are enabling more women than ever before to beat breast cancer, and some 2.4 million survivors are alive today. Now a move is under way to determine just how many women are vulnerable to heart disease because of their cancer battle, and how to help them.
Chemo is only one cardiac culprit. Other factors play a role, too: Chest radiation, the weight gain that plagues many survivors, physical inactivity during treatment and stress.
"In the process of curing their breast cancer, we've exposed them to some pretty nasty things. And it's not just one nasty thing, it's a sequence of nasty things," explains Dr. Pamela Douglas, a Duke University cardiologist who is planning research into how to protect these women's hearts.
"This is really coming at you from all sides," says Douglas, who outlined the "multiple hits" in this month's Journal of the American College of Cardiology.
But much of the debate centers on who should use anthracyclines, including the best-known Adriamycin, that can damage heart muscle, sapping its pumping strength.
Dr. Dennis Slamon of UCLA's Jonsson Cancer Center cites nine studies, here and abroad, that conclude that only the 20 percent of patients whose tumors have an overactive gene called Her2 are specifically sensitive to anthracyclines.
Then Slamon's closer inspection found that not all Her2 patients are alike — and only those who have a second overactive gene, called TopoII, derive special benefit from anthracyclines. That's about 8 percent of breast cancer patients.
The powerful Her2-targeting drug Herceptin — key for women with Her2-positive tumors — also comes with a heart-damage warning. But adding it to anthracyclines increases the heart risk fivefold, with no extra benefit, Slamon found.
Outright heart failure during chemo is rare, around 2 percent of patients. But Douglas cites research that anywhere from 10 percent to half of anthracycline users experience more subtle heart weakening, making them more vulnerable to aging's usual rigors, like high blood pressure and cholesterol.
And in this month's Journal of Clinical Oncology, researchers tracked breast cancer survivors ages 66 to 70 who had undergone chemo 10 years earlier. Those who had received an anthracycline were 26 percent more likely to have developed heart failure in the following decade than those on different chemo.
"It's almost like the perfect storm," Slamon says of all the research. "We're adding no incremental benefit with plenty of incremental toxicity."
Now the influential National Breast Cancer Coalition is lobbying oncologists and government regulators to reconsider treatment guidelines.
"These are very strong, very real data that they need to pay attention to," says coalition president Fran Visco.
But many oncologists aren't convinced, and want more evidence that other chemos work as well.
Indeed, Duke University is beginning a major study funded by the Defense Department to do additional genetic testing on Her2-negative women, to compare Adriamycin to the non-anthracycline Taxotere.
"It's fair to say I'm using less Adriamycin for truly early stage" cancer, says lead researcher Dr. Kelly Marcom, Duke's breast oncology chief.
"But there are still patients that I think have cancers that may be more sensitive to Adriamycin," Marcom adds. The jury is still out."
However that controversy ends, a bigger question is how to find and help survivors with heart damage from any cause. As Jane Sartin of Providence, N.C., learned, symptoms are sneaky.
Sartin underwent a mastectomy for side-by-side breast tumors, and took Adriamycin followed by Herceptin. She was warned about heart side effects, and knew as an overweight smoker she already was at risk. Yet she blamed the surgery when she got winded.
"I had never said anything to my doctor about it. I'd say, 'I'm tired, I think from the surgery,'" recalls Sartin, 45.
Twice her ejection fraction — a measure of blood pumped per beat — dropped well below normal. It bounced back with treatment changes, and Sartin believes her cancer therapy's benefit justified the side effect.
"I really felt like, hey, I can deal with anything as long as I'm alive," says Sartin, who now is dieting and weaning herself from cigarettes.
For now, never shrug off heart-related symptoms, stresses Dr. Ann Bolger of the University of California, San Francisco, an American Heart Association spokeswoman. Early care can be lifesaving.
Duke's Douglas recommends that all breast cancer patients get a formal heart risk assessment before oncologists decide final treatment. It might sway cancer therapy, or signal who'll need extra heart care later.