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Does Taking Beta Blockers Affect HER2-Positive Breast Cancer Survival?

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There may be a link between taking beta blockers, a heart medicine, before being diagnosed with advanced-stage HER2-positive breast cancer and worse survival after being treated with anti-HER2-medicines, a study suggests.

The research was published online on July 14, 2020, by Frontiers in Oncology. Read “The Influence of Pre-Existing Beta-Blockers Use on Survival Outcomes in HER2 Positive Advanced Breast Cancer: Pooled Analysis of Clinical Trial Data.”

HER2-positive breast cancer treatments and heart problems

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 1 out of every 4 breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive and may be harder to treat than HER2-negative breast cancers.

There are a number of anti-HER2 medicines used to treat HER2-positive breast cancer. Many of these medicines — including Herceptin (chemical name: trastuzumab) and its biosimilars (medicines that are highly similar to Herceptin) — are known to cause heart problems, including reduced heart function and congestive heart failure. The risk of heart problems is higher if the anti-HER2 medicine is given in combination with anthracycline chemotherapy.

What are beta blockers?

Beta blockers, also called beta-andrenergic blocking agents, are medicines that reduce blood pressure. Beta blockers make your heart beat slower and with less force. Beta blockers also help open up your veins and improve blood flow.

Beta blockers are commonly used to treat:

  • irregular heartbeat, called arrhythmia by doctors
  • heart failure
  • chest pain, called angina by doctors
  • heart attacks

About the study

Because Herceptin and other anti-HER2 medicines can affect the heart, doctors may prescribe a beta blocker or other heart medicine during anti-HER2 therapy.

The researchers who did this study wanted to know if taking a beta blocker before anti-HER2 therapy for advanced-stage HER2-positive breast cancer affected survival.

The researchers gathered results from four large studies looking at treatments for advanced-stage HER2-positive breast cancer:

  • the CLEOPATRA study, looking at adding Perjeta (chemical name: pertuzumab) to Herceptin and Taxotere (chemical name: docetaxel) compared to Herceptin and Taxotere alone
  • the EMILIA study, comparing Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) to the combination of Tykerb (chemical name: lapatinib) and Xeloda (chemical name: capecitabine)
  • the TH3RESA study, comparing Kadcyla to the doctor’s treatment of choice
  • the MARIANNE study, comparing Kadcyla alone, Kadcyla and Perjeta, and Herceptin plus taxane chemotherapy

All the people in the four studies were diagnosed with advanced-stage HER2-positive breast cancer. People in the EMILIA study who were treated with either Kadcyla or Tykerb and Xeloda and people in the TH3RESA study who were treated with the doctor’s choice of treatment were not included in this analysis. They were excluded because the researchers wanted to look at the survival outcomes of people who were being treated with a beta blocker and Herceptin, Perjeta, and Kadcyla, all of which are known to cause heart problems.

For this analysis, the researchers looked at survival outcomes for 2,777 people in the four studies. Of the people in the analysis, 266 were taking a beta blocker when they started treatment with an anti-HER2 medicine. The most common beta blockers taken were:

  • Zebeta (chemical name: bisoprolol): 68 people
  • Tenormin (chemical name: atenolol): 67 people
  • Lopressor/Toprol XL (chemical name: metoprolol): 57 people
  • Coreg (chemical name: carvedilol): 23 people
  • Inderal/InnoPran XL (chemical name: propranolol): 21 people

Of the 266 people taking a beta blocker when they started anti-HER2 therapy:

  • 60 were in the CLEOPATRA study
  • 103 were in the MARIANNE study
  • 51 were in the EMILIA study
  • 52 were in the TH3RESA study

The results showed that people taking a beta blocker when they started anti-HER2 therapy were about 27% more likely to have worse survival than people who weren’t taking a beta blocker when they started anti-HER2 therapy. This result was the same for people who had preexisting heart disease.

“In large high-quality data, pre-existing use of beta blockers in HER2-positive advanced-stage breast cancer patients initiating anti-HER2 therapies was independently associated with worse overall survival,” the researchers concluded. “The finding is contrary to pre-study hypotheses, findings in other breast cancer subtypes, and emerging preclinical data for effects of beta blockers on cancer. While this study does not justify the cessation of beta blockers, and cardiovascular disease should continue to be appropriately treated within HER2-positive advanced-stage breast cancer, the study presents important evidence that the effect of beta blockers may not be the same between cancers or breast cancer subtypes — with the impact potentially being negative within HER2-positive advanced-stage breast cancer. Future research is urgently required to validate findings in large real-world databases and prospective studies.”

What this means for you

If you’re taking a beta blocker for a preexisting heart condition and have been diagnosed with advanced-stage HER2-positive breast cancer, you may want to talk to your doctor about this study. You may be able to take a different heart medicine while you’re being treated with an anti-HER2 medicine.

It’s very important that you don’t abruptly stop taking a beta blocker. Doing so may increase your risk of a heart attack or other heart problem.

Together, you and your doctor will weigh the pros and cons of all the medicines you are taking and decide on the best treatment plan for your unique situation.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser


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