Breast cancer patients who take either of two heart medicines while undergoing treatment with Herceptin (trastuzumab) were not protected from the cardiac damage that is a common side effect of Herceptin therapy. This is according to a large, randomized clinical trial presented Sunday, March 11, 2018, at the American College of Cardiology’s 67th Annual Scientific Session in Orlando, Florida.
But the patients did benefit from either of the two common heart drugs if they had already undergone treatment with drugs called anthracyclines before starting Herceptin, or if they were being treated with anthracyclines and Herceptin at the same time. Anthracyclines, such as Adriamycin or Rubex (doxorubicin), are chemotherapy drugs. Both anthracyclines and Herceptin are significant medicines for managing a common type of breast cancer called HER2-positive breast cancer.
The study is one the first and the largest to explore whether cardiac medication can prevent heart damage linked to Herceptin. Heart damage caused by various types of breast cancer medication, such as Herceptin, has been a vexing problem in oncology and sometimes prevents patients from completing a full course of cancer treatment. The new study should give doctors more confidence in recommending both anthracycline-based chemotherapy and Herceptin — along with a cardiac medication — to patients with HER2-positive breast cancer.
“Herceptin is such a powerful anti-cancer drug, we need to do whatever it takes to provide patients with this choice,” says study chair Maya E. Guglin, MD, of the University of Kentucky's Gill Heart and Vascular Institute in Lexington.
A Critical Drug for HER2-Positive Breast Cancer
About 20 to 25 percent of women diagnosed with breast cancer have HER2-positive cancer. Herceptin is considered the gold standard treatment for HER2-positive breast cancer. Previous research published in the New England Journal of Medicine showed that adding Herceptin to standard chemotherapy treatment led to a 52 percent reduced risk of recurrence and a 33 percent improvement in survival.
But about one in four women treated with Herceptin develop heart problems, and some women must interrupt or stop the treatment if heart function declines too much. During Herceptin treatment, which is recommended for one year, toxicity can cause the heart to become too weak to pump blood. All patients on Herceptin undergo regular cardiac tests, such as an echocardiogram, to look for possible heart damage.
“Typically with breast cancer treatment, so many women experience some decline in cardiac function,” Dr. Guglin says. “The heart becomes somewhat weaker. Sometimes it’s associated with the symptoms of heart failure. But most frequently, it’s a decline in ejection fraction, which is a measure of cardiac function.”
If tests show reduced heart function, “doctors tend to stop Herceptin and not restart it until the next checkup shows the heart has healed. It is a big anxiety for these women because every three months they have to go through some type of cardiac testing, and if damage is found, they have to stop this lifesaving treatment.”
Related: How to Manage Side Effects of Advanced Breast Cancer Treatment
Patients Previously Treated With Chemotherapy Benefit
The 167-site study included 468 patients with HER2-positive breast cancer beginning treatment with Herceptin. All of the patients had normal heart function and were not taking ACE (angiotensin-converting enzyme) inhibitors or beta-blockers — both heart drugs — at the time of enrolling in the study. Half of the study participants had already received anthracyclines or were receiving anthracyclines concurrently with Herceptin. The 468 patients were then assigned to one of three regimens: receiving Zestril (lisinopril), which is an ACE inhibitor, Coreg (carvedilol), which is a beta-blocker, or a placebo. The study participants, whose average age was 51, were followed for two years.
The study showed that neither Zestril nor Coreg prevented heart damage in the patients who were receiving Herceptin only. But in patients who also received anthracyclines such as Adriamycin, the drugs reduced the risk of heart damage. In these patients, cardiac event rates in the placebo group were 47 percent, compared with 37 percent in patients taking ACE inhibitors and 31 percent in patients taking beta blockers.
"The data clearly demonstrated that, for patients with HER2-positive breast cancer taking both anthracyclines and Herceptin, adding either an ACE inhibitor or a beta-blocker to the treatment regimen can significantly offset the chance of heart problems," Guglin says.
The findings suggest that heart damage likely begins with anthracycline therapy and is aggravated by Herceptin therapy, Guglin explains.
“Anthracyclines do some subtle damage to the cardiac muscles,” Guglin says. “All these patients in the study were checked before they started on Herceptin; they were only included if their cardiac function was normal. Obviously, if you put Herceptin on top of pre-existing heart damage, it suddenly shows up.”
Study May Change the Way Women Are Treated Going Forward
It’s disappointing that adding cardiac medication failed to help prevent heart damage in patients who take Herceptin only, says Bonnie Ky, MD, an assistant professor of medicine at the University of Pennsylvania in Philadelphia. But the research points to a way of reducing heart damage while allowing patients to utilize Herceptin, which has proven to be a lifesaving medication.
When Herceptin came on the market in 1998 “it was a hit,” Dr. Ky says. “For women who have this HER2-positive breast cancer, Herceptin is a key to long-term survival and long-term well-being. So you hate to expose them to something that interrupts their treatment.”
The study results have the potential to change the standard of care for patients with HER2-positive breast cancer, Guglin says. In recent years, oncologists have been reluctant to recommend anthracycline-based chemotherapy due to the growing recognition that the drugs are linked to heart damage.
“The most important conclusion is you can treat patients with anthracyclines first and then Herceptin,” she says. “This is the most effective algorithm for breast cancer. You may be more effective at preventing cardiac damage with either of these cardiac medications. These [heart medications] are extremely well-established and available. Most practitioners are comfortable with them.”