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HER2 testing for stomach cancer

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on May 23, 2022.

If you’re newly diagnosed with stomach or gastrointestinal cancer, your doctor may suggest sending your biopsy sample for HER2 testing.

The testing, performed in a laboratory, tells you and your care team more about the cancer and how it’ll progress and react to different treatments.

Learn more below about the HER2 gene and protein, the testing process, what you can expect, and how to read your HER2 testing report.

What is HER2 testing?

HER2 testing analyzes the cancerous cells from your biopsy to see how much HER2 protein they’re making and how many copies of the HER2 gene they have.

This testing may also be called:

  • HER2/neu test
  • Human epidermal growth factor receptor 2 test

HER2 is a growth factor receptor, a normal protein expressed in healthy cells. It takes in signals from other parts of your body and tells cells to grow.

But having too much HER2 in the cancer cells can lead to worse outcomes. Large amounts of HER2 protein or too many copies of the HER2 gene help cancers grow quickly and make them more likely to spread.

Knowing the cancer’s HER2 status isn’t just important for your prognosis. Researchers have developed drugs that target these mechanisms the cancer uses to grow, so a HER2-positive cancer will have additional opportunities for targeted and immunotherapy treatments.

Which stomach cancer patients need HER2 testing?

Some stomach (gastric) and gastroesophageal cancers are fueled by HER2. Estimates for how prevalent HER2 overexpression is in gastric cancers range from about 7 percent to 34 percent, according to a review in the Journal of Cancer Research and Clinical Oncology. This is a relatively new field of study and testing is still in the works for stomach cancers, so those estimates may become more firm in time.

Many of the current HER2 targeted therapies are used only against advanced (stage 4) cancers that can’t be surgically removed or that have returned after treatment, so your care team will likely hold off on a HER2 test if the cancer is in the early stages due to the cost and difficulty of the procedure.

Higher-than-usual levels of HER2 protein or gene copies are possible characteristics of many other cancers too, including:

How does the HER2 test work?

HER2 testing is done on a biopsied sample of the cancer. You shouldn’t need a new biopsy for this procedure.

Biopsies for stomach cancer are typically taken during an endoscopy or other imaging tests, when doctors already have an endoscope in the area. Your care team uses a tool at the end of the lighted tube of the endoscope to take a sample of an abnormal area of the stomach lining that they think could be cancerous.

They may also use an ultrasound machine along with the endoscope and a thin needle to take a deeper sample.

The samples are sent to a lab, where a pathologist treats the cancer cells with special dyes to visualize different characteristics of the tumor.

These dyes are one of two types:

  • Immunohistochemistry (IHC), which uses antibodies to label the HER2 protein in the sample.
  • Fluorescence in situ hybridization (FISH), which uses a short piece of DNA labeled with fluorescent dye. This DNA matches to HER2 genes in the cells, labeling them and giving off light that a machine can detect.

What do my HER2 test results mean?

The results from your HER2 testing can be found in a pathologist’s report. Positive HER2 test results mean that there are larger-than-normal amounts of HER2 protein or too many copies of the HER2 gene in the cancer cells.

Immunohistochemistry is usually done first. The IHC results are graded from 0 to 3+ depending on the level of HER2 protein. Below, find what the numbers mean:

  • Cancers that get a 0 or 1+ are rated as HER2-negative.
  • Cancers that get a 2+ are ambiguous, so the pathologist typically performs FISH testing to determine whether the cancerous cells have additional copies of the HER2 gene.
  • Cancers that get a 3+ are HER2-positive.

A positive HER2 test result opens up several targeted treatment options for cancer.

  • The monoclonal antibody therapy Herceptin® (trastuzumab) and similar drugs block the HER2 receptor, slowing the growth signals being sent to the stomach cancer. Adding this drug to a chemotherapy regimen may help patients with advanced HER2-positive stomach cancer live longer than they would on a chemotherapy-only regimen.
  • Another antibody-based drug, Enhertu® (fam-trastuzumab deruxtecan-nxki), uses the trastuzumab antibody to home in on the cancer cells and deliver a chemotherapy drug payload directly to them. This is called an antibody-drug conjugate (ADC). It’s typically used to treat advanced HER2-positive stomach cancer after patients have tried trastuzumab.

Additional drugs targeting HER2 are being tested in clinical trials. These include:

  • Traditional small-molecule drugs, such as Tykerb® (lapatinib)
  • Antibodies such as Perjeta® (pertuzumab) and Margenza® (margetuximab-cmkb)
  • New ADCs, including Kadcyla® (ado-trastuzumab emtansine)

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