Breast cancer survivors may face increased risk of heart disease — and doctors are debating whether it is time largely to abandon a chemotherapy mainstay that is one reason.
Drugs called anthracyclines are a breast chemo staple despite a well-known risk: They weaken some women's hearts. What is new is research that suggests the drugs work no better than safer alternatives for most women.
It is a controversy born of success: Treatment advances are allowing more women than ever to beat breast cancer, and some 2.4 million survivors are alive in the United States today. Now a move is under way to determine just how many are vulnerable to heart disease because of their cancer battle and how to help those who are.
Chemo is only one cardiac culprit. Other factors play a role, too: Chest radiation, weight gain that plagues many survivors, physical inactivity during treatment, 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," said 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," said 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 and sap the organ's pumping strength.
Dr. Dennis Slamon of UCLA's Jonsson Comprehensive Cancer Center cites nine studies, in the United States and abroad, that conclude 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 not all Her2 patients are alike - and only those who have a second overactive gene, called TopoII, derive special benefit from anthracyclines. That is about 8 percent of breast cancer patients.
The powerful Her2-targeting drug Herceptin - crucial 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. Douglas cites research that found from 10 percent to half of anthracycline users experience more subtle heart weakening, however, which makes them more vulnerable to aging's usual rigors, like high blood pressure and cholesterol.
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 are not 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 nonanthracycline 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," he 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 patient Jane Sartin 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 every breast cancer patient get a formal heart risk assessment before oncologists decide final treatment. It might sway cancer therapy, or signal patients who would need extra heart care later.