The HER2 Advocate’s Toolkit: How to Talk to Your Doctor About Your Specific Mutation

Learning that your lung cancer has a HER2 change can bring up a lot of questions. HER2 (also called ERBB2) is a gene that can play a role in some non-small cell lung cancers. Knowing your exact result helps you and your doctor choose the right path. This guide gives you questions to bring to your next visit.¹

Why your specific HER2 result matters

HER2 shows up in lung cancer in more than one way, and the details matter. Your care team may talk about a HER2 mutation, a HER2 amplification (extra copies of the gene), or extra HER2 protein on the cancer cells. Each one means something different, and not all of them are treated the same way.^1-4

Right now, targeted treatment is approved for people whose tumors have a certain kind of HER2 mutation in the part of the gene called the tyrosine kinase domain, often an exon 20 insertion. That is why the wording on your report matters. Ask your doctor to explain your result in plain terms so you understand which group you are in.^1,2

Questions to ask about your diagnosis and mutation

Bring these questions to help you understand your result:^1,3,4

• What exact HER2 change do I have? Ask whether it is a mutation, an amplification, or extra protein, and where it was found.
• What test was used to find it? Common tests include next-generation sequencing (NGS) of tumor tissue and, in some cases, a blood test called a liquid biopsy.
• Was I tested for other biomarkers too? HER2 changes usually do not appear alongside other main drivers, so full testing helps rule others out.
• Can you write down my result? A copy of your report helps if you seek a second opinion.

Questions to ask about your treatment options

Treatments work differently for each person, so ask your doctor which options are best for your specific results. Approved and studied options for HER2-changed non-small cell lung cancer include:^1,2,5,6

• Fam-trastuzumab deruxtecan (Enhertu®) – A targeted therapy given through an IV. It is approved for certain HER2 mutations and may be used for some HER2 amplifications after earlier treatment. It carries a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because it can cause serious lung inflammation (interstitial lung disease or pneumonitis) and can harm an unborn baby.
• Zongertinib (Hernexeos®) – A targeted pill approved for adults with advanced non-small cell lung cancer that has HER2 tyrosine kinase domain-activating mutations, as detected by an FDA-authorized test. In 2026, its approval was expanded to include people who have not yet had treatment for advanced disease.
• Sevabertinib (Hyrnuo®) – A targeted pill for adults with advanced non-squamous non-small cell lung cancer that has HER2 tyrosine kinase domain activating mutations, after prior treatment.
• Ado-trastuzumab emtansine (Kadcyla®) – Approved for breast cancer and sometimes used for HER2-positive lung cancer. This drug also carries a boxed warning. It has this warning because it can harm the liver, heart, and an unborn baby.
• Chemotherapy with or without immunotherapy – Often used first for advanced disease, sometimes followed by a targeted therapy.

Some treatments listed here are not approved by the FDA to treat lung cancer. They may be approved for other conditions. A doctor may prescribe them “off-label” when evidence suggests they help. Talk to your doctor about what is right for you.

Helpful questions include:

• What is the goal of this treatment?
• What are the possible side effects?
• What other options do I have?
• You can also ask if a clinical trial is a good fit.

Questions to ask about side effects and daily life

Every treatment can cause side effects, and they vary depending on the specific drug you take. Ask your doctor what to expect and when to reach out to your care team. You should also call your doctor if you have any changes that concern you during treatment.

Before starting treatment, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs. It is a good idea to ask about seeing a supportive or palliative care doctor early to help manage side effects.¹

Getting a second opinion and finding support

Research in this area is moving quickly, so your doctor should be up to date on the newest recommendations for your type of lung cancer. If you do not feel comfortable with the answers you get, it is okay to seek a second opinion. A specialized cancer center can offer testing and treatment experience that may open more options.^1,3

You do not have to face this alone. Ask about lung cancer support communities, patient and caregiver mentors, and groups for people with HER2 changes.¹

Talk to your doctor

You are the most important member of your care team. Bring these questions, ask for your results in writing, and keep asking questions until you understand your options.