People With Metastatic HER2-Low Breast Cancer Report How Enhertu Affected Their Quality of Life

People With Metastatic HER2-Low Breast Cancer Report How Enhertu Affected Their Quality of Life

Patient-reported outcomes from the DESTINY-Breast04 study, which looked at using the targeted therapy Enhertu to treat metastatic HER2-low breast cancer, suggest Enhertu controls pain better than doctors’ choice of chemotherapy.
Sep 14, 2022.

Patient-reported outcomes from the DESTINY-Breast04 study, which looked at using the targeted therapy Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) to treat metastatic HER2-low breast cancer, suggest Enhertu controls pain better than doctors’ choice of chemotherapy.

The research was presented at the European Society for Medical Oncology (ESMO) Congress 2022 on Sept. 11, 2022.

Metastatic breast cancer is breast cancer that has spread to parts of the body away from the breast, such as the bones, liver, or brain.

Naoto Ueno, MD, professor of breast medical oncology at the University of Texas MD Anderson Cancer Center, recently joined The Podcast to discuss the research from the DESTINY-Breast04 study.


About HER2-low breast cancer

Some breast cancer cells make, or overexpress, too many copies of the HER2 gene. The HER2 gene makes a protein known as a HER2 receptor. HER2 receptors are like ears, or antennae, on the surface of cells. These HER2 receptors receive signals that stimulate the cell to grow and multiply. But breast cancer cells with too many HER2 receptors can pick up too many growth signals and start growing and multiplying too much and too fast. Breast cancer cells that overexpress the HER2 gene are called HER2-positive.

Doctors use several tests to find out if a breast cancer is HER2-positive. Two of the most common are:

IHC (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample and gives it a score of 0 to 3+. If the score is 0 to 1+, it’s considered HER2-negative. If the score is 2+, it’s considered borderline. A score of 3+ is considered HER2-positive.

FISH (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result zero).

About 15% to 20% of breast cancers are HER2-positive. Still, research shows that more than 60% of breast cancers considered HER2-negative have some HER2 proteins on the surface of its cells. There just aren’t enough HER2 proteins for the cancer to be considered HER2-positive. Doctors now call these cancers HER2-low.

There are medicines called targeted therapies that specifically target the HER2 receptors on HER2-positive breast cancer cells. Herceptin (chemical name: trastuzumab) was the first anti-HER2 medicine developed. Still, these anti-HER2 medicines have not been effective against HER2-low breast cancers.

HER2-low breast cancer has commonly been treated as if it were HER2-negative breast cancer, almost always with chemotherapy.


About the DESTINY-Breast04 study

The DESTINY-Breast04 study included 557 people — 555 women and two men — diagnosed with metastatic HER2-low breast cancer. All the people in the study had already received one or two lines of chemotherapy for metastatic disease.

In the study, the researchers defined breast cancer as HER2-low if it got an IHC score of 1+ or an IHC score of 2+ and a negative FISH test.

The researchers compared Enhertu and doctors’ choice of chemotherapy to see which was more effective. The results showed that Enhertu was the more effective treatment — it doubled progression-free survival and improved overall survival.

Progression-free survival is how long people live without the cancer growing. Overall survival is how long people live, whether or not the cancer grows.

In August 2022, the U.S. Food and Drug Administration (FDA) approved Enhertu to treat unresectable or metastatic HER2-low breast cancer that has been previously treated with chemotherapy:

  • for metastatic disease

  • after surgery for early-stage disease that came back (recurred) within six months of completing chemotherapy

Unresectable means the cancer can’t be removed with surgery.


Patient-report outcomes from DESTINY-Breast04

The survival results from the DESTINY-Breast04 study were practice changing. Still, the researchers wanted to ask the people in the study how Enhertu or chemotherapy affected their quality of life.

The researchers used three proven questionnaires to assess people’s quality of life before, during, and after treatment. The questionnaires asked the people:

  • how they perceived their overall health

  • how difficult it was to carry out everyday tasks

  • if there were any symptoms or side effects and how severe they were

The researchers found that the quality of life of people receiving Enhertu did not deteriorate as fast as the quality of life of people receiving chemotherapy.

“The Enhertu treatment delays the deterioration of quality of life, which means that when the treatment is working very well, patients could maintain a reasonable quality of life, much better compared to people who are receiving regular chemotherapy,” Dr. Ueno told “So, that’s where the excitement is because we know that this treatment is effective, we know that it is safe, and the question is, does the patient feel the same way based on the good efficacy and safety, and we have shown that it does help the patient to maintain a reasonable quality of life by receiving this treatment compared to standard chemotherapy.”

The results also showed that people receiving Enhertu had 16.4 months before pain negatively affected their quality of life, versus 6.1 months for people receiving chemotherapy.

Still, people who received Enhertu had more nausea and vomiting when they started treatment than people who received chemotherapy. But Dr. Ueno pointed out that this difference leveled out as treatment went on, so there was no difference between the treatments overall.

Nausea is a known side effect of Enhertu, so most people who receive it also take anti-nausea medicine preventively.

“Compared to chemotherapy, patients generally did much better on Enhertu,” Dr. Ueno said. “From the perspective of pain, physical functioning, emotional functioning, social functioning, fatigue — everything — the results favored Enhertu compared to chemotherapy.”


What this means for you

If you’ve been diagnosed with metastatic breast cancer or early-stage breast cancer that can’t be removed with surgery, you may want to talk to your doctor about the HER2 test results in your pathology report. If the score was 1+ on an IHC test or the score was 2+ on an IHC test plus a negative FISH test, Enhertu may be an option for you.

The results of this study offer the promising news that if you do receive Enhertu, your quality of life can be as good or better than it might be if you were receiving chemotherapy.

Learn more about Enhertu.

Written by: Jamie DePolo, senior editor

— Last updated on September 23, 2022, 6:55 PM

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