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Heart Medicines Seem to Reduce Risk of Serious Cardiac Damage in Women Taking Herceptin

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Herceptin (chemical name: trastuzumab) is a targeted therapy used to treat HER2-positive breast cancer. Heart problems, including heart muscle damage and heart failure, are possible serious side effects of Herceptin.

A small study suggests that heart medicines, such as beta blockers or ACE inhibitors, taken along with Herceptin, can reduce the risk of serious heart damage in women diagnosed with early-stage, HER2-positive breast cancer.

The research was published online on Nov. 29, 2016 by the Journal of Clinical Oncology. Read “Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity.”

HER2-positive breast cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive and harder to treat than HER2-negative breast cancers.

Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals. Herceptin, which is given intravenously, is approved by the U.S. Food and Drug Administration (FDA) to:

  • treat advanced-stage, HER2-positive breast cancers
  • lower the risk of recurrence (the cancer coming back) of early-stage, HER2-positive breast cancers with a high risk of recurrence.

Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk) is an injectable form of Herceptin

Herceptin is often given at the same time as or right after chemotherapy. In many cases, the chemotherapy regimen may include an anthracycline.

Anthracycline chemotherapy medicines are:

  • Adriamycin (chemical name: doxorubicin)
  • Ellence (chemical name: epirubicin)
  • Doxil (chemical name: liposomal doxorubicin)
  • daunorubicin (brand names: Cerubidine, DaunoXome)
  • mitoxantrone (brand name: Novantrone)

Anthracyclines work by damaging cancer cells’ genes and interfering with their reproduction. Anthracyclines also can cause heart problems.

In this Canadian study, 94 women diagnosed with early-stage, HER2-positive breast cancer who were being treated with Herceptin were randomly assigned to one of three treatments along with Herceptin:

  • bisoprolol, a beta blocker that is used to treat high blood pressure and other heart conditions; it works by relaxing blood vessels and slowing the heart rate (31 women)
  • perindopril, an ACE inhibitor that is used to treat high blood pressure and other heart conditions; it works by preventing the production of certain chemicals in the body that tighten the blood vessels which makes the blood flow more smoothly (33 women)
  • placebo, a dummy pill that looked just like the other medicines (30 women)

The women had similar heart function before the study started. The researchers followed the women for 5 years.

To see if the beta blocker or ACE inhibitor helped prevent heart damage, the researchers did MRI imaging of the women’s hearts before the study started and after the women stopped taking the Herceptin and heart medicines or placebo.

The images showed that women who took bisoprolol, the beta blocker, had fewer signs of heart problems than women who took the placebo and women who took perindopril, the ACE inhibitor. Women who took perindopril had fewer signs of heart problems than women who took the placebo.

The researchers reported that the heart medicines were well tolerated and there were no serious side effects.

Ian Paterson, associate professor of medicine at the University of Alberta and cardiologist at the Mazankowski Alberta Heart Institute who was the lead author of the study, said that bisoprolol and perindopril seem to safeguard against damage to the heart, as well as allow women to stay on Herceptin without interruption. If a person receiving Herceptin shows signs of heart weakening, treatment is stopped until heart function returns to normal. This pause in treatment can last for a month or two.

"We are aiming for two outcomes for these patients -- we're hoping to prevent heart failure and we're hoping for them to receive all the chemotherapy that they are meant to get, when they are supposed to get it -- to improve their odds of remission and survival,” Paterson said.

"We think this is practice-changing," said Edith Pituskin, also of the University of Alberta and co-investigator of the study. "This will improve the safety of the cancer treatment that we provide."

If you’ve been diagnosed with early-stage, HER2-positive breast cancer and will be treated with Herceptin, you may want to talk to your doctor about this study, as well as your personal risk of treatment-related heart problems. You might want to ask if visiting a cardiologist before treatment starts is a good idea for you. The cardiologist can evaluate your heart function and decide if you’re at risk of developing heart problems from breast cancer treatment and whether a beta blocker or ACE inhibitor makes sense for you. Together, you can decide on the best treatment plan for your unique situation.

Editor’s Note: This article was updated with information about Herceptin Hylecta, which the FDA approved on Feb. 28, 2019.

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