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  7. HER2

HER2 and Lung Cancer

Testing for HER2 gene mutations helps your doctor understand your lung cancer and inform you of all of your treatment options.

HER2 at a Glance:

  • Errors in the HER2 gene are one type of lung cancer biomarker.
  • Comprehensive biomarker testing can help match you to specific treatments that are available, including chemotherapy, immunotherapy, and targeted therapy.
  • You can ask for comprehensive biomarker testing at diagnosis or if treatment stops working. 

Frequently Asked Questions about Biomarker Testing

What Is HER2?

HER2 (also known as ERBB2) is a signaling receptor in the cell. It belongs to a family of signaling receptors that also includes EGFR, so sometimes you may hear the two talked about together.  

Changes in the HER2 gene can cause cancer cells to grow or spread.

HER2 alterations in lung cancer can include:

  • HER2 mutations: Changes in the HER2 gene that can drive cancer growth.
  • HER2 amplifications: Having too many copies of the HER2 gene.
  • HER2 Overexpression: When the HER2 protein is expressed in high quantities on the surface of cancer cells.

Why HER2 Biomarker Testing Matters

HER2 testing is important because it shows whether your lung cancer has certain genetic changes. These changes can make your cancer act in a specific way and can also make it respond to treatments that are designed just for HER2‑positive tumors. Knowing your HER2 status helps your care team choose the most effective treatment plan for you.

Biomarker testing looks for specific genetic changes in the tumor to help guide treatment. Testing includes DNA-based tests to identify changes in the genes themselves, and RNA-based tests to measure how those genes behave, giving your care team a fuller picture of your tumor makeup and available treatment options.

How Is HER2 Testing Done?

Testing is usually done at diagnosis or when treatment changes. Your doctor will need to test your tumor through a tissue or blood (liquid) biopsy. There are several different types of tests that doctors use to look for changes, or biomarkers in your cells:

  • Fluorescence in Situ Hybridization, or FISH, analysis is a common genetic test. FISH analysis looks at changes in the chromosomes through tissue under a microscope.
  • Immunohistochemistry (IHC) looks for proteins in the cell under a microscope.
  • Next-generation sequencing (NGS), also called comprehensive biomarker testing, is when tissue from a patient's tumor (gathered from a biopsy) is placed in a machine that looks for many possible biomarkers at one time.
  • Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory method used to make many copies of a specific genetic sequence for analysis.

Your doctor may perform several of these tests at the same time to help confirm results. Different biomarkers rely more heavily on certain tests.

HER2 amplification is tested using fluorescence in Situ hybridization (FISH) or NGS, which can identify HER2 exon 20 insertions and other alterations. IHC can be used to look for HER2 overexpression.

Learn more about the different types of biomarker tests. 

Understanding Your HER2 Test Results

A HER2‑positive result means your cancer has a specific genetic change that can be treated with targeted therapies designed for HER2‑mutant lung cancer.

A HER2‑negative result means your cancer does not have a HER2 mutation, so HER2‑targeted treatments are unlikely to help.

An unclear result means the test couldn’t confirm whether a HER2 mutation is present, and your care team may recommend repeat or more comprehensive testing. 

How HER2 Results Influence Treatment

A HER2-positive test result may affect your treatment options. Recommendations depend on the type of HER2 alteration identified, the stage of cancer, previous treatments, and your overall health.

Right now, treatment is available for patients who have a type of HER2 mutation called a HER2 exon 20 insertion mutation. 

First-Line Treatment

Treatment for advanced-stage lung cancer with this mutation is chemotherapy with or without immunotherapy, or targeted therapy (Zongertinib) as a first-line therapy. 

Additional Treatment Options

Subsequent treatments can include oral targeted therapies or intravenous medications like fam-trastuzumab deruxtecan (Enhertu).

Some patients may receive a different targeted drug called ado-trastuzumab emtansine (Kadcyla), which is approved for breast cancer but sometimes used in HER2-positive lung cancer. 

Zongertinib (Hernexeos), is a kinase inhibitor, for adults with unresectable or metastatic NSCLC, whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. 

Sevabertinib (Hyrnuo) is available for the treatment of adult patients with locally advanced or metastatic, nonsquamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. 

Treatment for advanced-stage HER2 amplification depends on the amount of HER2 in the tumor. Some patients may receive fam-trastuzumab deruxtecan (Enhertu) after prior treatment with chemotherapy (with or without immunotherapy).

Many other HER2-targeted medications are being studied in clinical trials. Ask your doctor if a clinical trial is right for you.

Dr. Justin Gainor discusses the strategies available to treat the HER2 biomarker in lung cancer. This video was produced in 2021. For the latest treatment options, speak with your doctor.

Video transcript

Questions to Ask Your Doctor

Work with your doctor to discuss your goals and options each time you have to review and interpret test results to make a treatment decision. The three big questions to ask are:

  • What is the goal of this treatment?
  • What are the potential side effects?
  • What other options do I have?

Research is happening at a rapid pace, and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.

What to Do After a HER2 Diagnosis

Someone with a HER2‑positive lung cancer diagnosis can take several empowering steps to stay ahead of their care. These are general medical information steps, not personal medical directives, and it’s important to work closely with a qualified healthcare professional for decisions about diagnosis or treatment. 

This helps confirm the exact HER2 change and shows whether there are any other markers that could guide treatment. 

Ask your care team which therapy is right for your specific HER2 alteration and what other options or clinical trials might be available. 

Writing down how you feel helps your team adjust treatment early and protects your quality of life.

Some HER2‑targeted treatments can affect these areas, so regular check‑ins help keep you safe.

If the cancer changes, repeat biomarker testing can show new information that guides the next treatment step.

Research in HER2‑positive lung cancer is moving quickly, and trials may offer access to promising new therapies.

Bring questions, take notes, and share what matters most to you, so your treatment plan fits your goals and preferences.

Support for People with HER2-Positive Lung Cancer

Lung cancer research can move at a rapid pace. Always speak with your doctor about the most up-to-date treatment guidelines.

Medically reviewed by: Jorge Gomez, MD

Last reviewed: June, 2026 

Page last updated: August 12, 2026

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