EGFR: Definition

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EGFR stands for epidermal growth factor receptor. It is a gene that provides the instructions for making a protein found on the surface of many normal cells. This protein acts as a receptor, meaning it receives signals from outside the cell that tell the cell when to grow and divide.

EGFR is an important biomarker. A biomarker is a measurable feature of a tumor, such as a gene change or an abnormal protein, that helps doctors understand how a cancer behaves and which treatments are most likely to work. EGFR matters most in lung cancer, where finding a change in the EGFR gene can open the door to treatments that work very differently from standard chemotherapy.

This article explains what EGFR is, how it is tested, what the results mean, and which treatments target it. For a fuller discussion in lung cancer specifically, see the guide on EGFR mutations in lung cancer.

What does EGFR do in normal cells?

In healthy cells, the EGFR protein helps control normal growth and repair. When a growth signal from outside the cell attaches to EGFR on the cell surface, the receptor switches on and sends a message inside the cell telling it to grow or divide. Once the message has been delivered, the receptor switches off again. This on-and-off control is what keeps normal tissue growing only when it needs to.

How do EGFR changes lead to cancer?

Cancer can develop when the growth signals inside a cell are no longer properly controlled. In some tumors, the EGFR gene becomes mutated, meaning its DNA instructions have changed. Certain mutations cause the EGFR protein to stay switched on all the time, even when no growth signal is present. The cell then keeps growing and dividing without normal control, and a tumor can form.

EGFR mutations in cancer are almost always acquired, meaning they develop in tumor cells during a person’s lifetime. They are not inherited from a parent and are not passed on to children.

Which cancers are tested for EGFR?

How EGFR is used differs from one cancer type to another, and this is a common source of confusion:

Lung cancer — This is where EGFR testing matters most. EGFR mutations are found most often in lung adenocarcinoma, and testing is standard for advanced non-small cell lung cancer. These mutations are more common in people who have never smoked or smoked very little, and in people of East Asian ancestry, although they can occur in anyone.
Colorectal cancer — Drugs that block the EGFR protein are used in advanced colorectal cancer, but the decision to use them is not based on testing EGFR itself. Instead, it depends on whether the tumor has changes in other genes, particularly KRAS, NRAS, and BRAF. Tumors with these changes are unlikely to respond to EGFR-blocking drugs. This is why a colorectal cancer report may discuss EGFR-targeted treatment without reporting an EGFR test result.
Head and neck cancer — An EGFR-blocking drug is used in some head and neck cancers. As in colorectal cancer, this is not decided by EGFR mutation testing.
Brain tumors — In glioblastoma, extra copies of the EGFR gene (called amplification) are common. Here, EGFR is used mainly to help confirm the diagnosis and classify the tumor, rather than to select a targeted treatment.

Not all cancers are tested for EGFR, and an EGFR result does not determine the stage of a cancer.

Why do pathologists test for EGFR?

EGFR is tested because it is a predictive biomarker, meaning the result helps predict whether particular treatments are likely to work. In lung cancer, several drugs are designed specifically to block abnormal EGFR signaling. These drugs work well when certain EGFR mutations are present, and are unlikely to help when they are absent. Testing EGFR therefore allows treatment to be matched to the biology of the individual tumor rather than chosen on the basis of the cancer type alone.

How do pathologists test for EGFR?

EGFR testing is usually performed on tumor tissue obtained during a biopsy or surgery. It can also be performed on a blood sample, often called a liquid biopsy, which looks for tumor DNA circulating in the bloodstream. A liquid biopsy is useful when a tissue sample is small, difficult to obtain, or when doctors need to check for new changes after treatment has started.

Standard testing methods include:

Polymerase chain reaction (PCR) — Looks for a defined set of specific, common EGFR mutations.
Next-generation sequencing (NGS) — Reads EGFR along with many other cancer-related genes at the same time, and detects a wider range of changes.
Immunohistochemistry — Measures the amount of EGFR protein rather than looking for gene mutations. It is used in some cancers but is not the standard way to select EGFR-targeted therapy in lung cancer.

How do EGFR results appear in a pathology report?

EGFR results usually appear in a section of the report called molecular testing, biomarker testing, or ancillary studies. Results are typically reported in one of these ways:

EGFR mutation detected — Followed by the name of the specific mutation. Genes are read in segments called exons, and the mutation name usually says which segment is involved. The two most common are an exon 19 deletion (a missing piece of the gene) and L858R in exon 21 (a single changed letter of the DNA code). These two are often called classical or common EGFR mutations, and they are the ones most likely to respond to EGFR-targeted drugs.
Exon 20 insertion detected — An extra piece of DNA has been added within exon 20. This is an important separate category, because these tumors usually do not respond well to the drugs used for the common mutations and are treated differently.
No EGFR mutation detected — Sometimes reported as EGFR wild type, meaning no change was found. EGFR-targeted drugs would not be expected to help, and treatment decisions are based on other findings.

Your report may also include a comment explaining whether the result makes EGFR-targeted therapy an option.

What treatments target EGFR?

Drugs that block EGFR are among the best established targeted therapies in cancer care. Which drug is considered depends on the specific mutation found.

For the common mutations (exon 19 deletion and L858R) in advanced lung cancer, there are currently several accepted first-line approaches, including osimertinib (Tagrisso) on its own, osimertinib combined with chemotherapy, and the combination of amivantamab (Rybrevant) with lazertinib (Lazcluze). Each has different benefits and side effects, and the choice depends on individual factors such as overall health and whether the cancer has spread to the brain. Older EGFR-blocking drugs, such as gefitinib (Iressa), erlotinib (Tarceva), and afatinib (Gilotrif), are still used in some situations. EGFR-targeted treatment may also be given after surgery in some earlier-stage lung cancers to lower the chance of the cancer returning.

For exon 20 insertions, treatment differs because these tumors respond poorly to the drugs above. Options include amivantamab combined with chemotherapy, and sunvozertinib (Zegfrovy) after chemotherapy has been tried.

In colorectal and head and neck cancers, the EGFR protein is blocked by a different class of drugs given by infusion, such as cetuximab (Erbitux) and panitumumab (Vectibix).

Over time, most cancers treated with EGFR-targeted drugs eventually stop responding, because the tumor develops new changes that get around the drug. When this happens, repeat testing on a new tissue sample or a liquid biopsy can sometimes identify the change responsible and point to the next treatment. Which of these options is appropriate is a decision made with the medical oncology team, based on the full pathology report and the individual clinical situation.

Questions to ask your doctor

Was my tumor tested for EGFR, and what did the test show?
If a mutation was found, which specific one was it?
Is my mutation one of the common types, or an exon 20 insertion?
Does my EGFR result make me eligible for EGFR-targeted therapy?
If several first-line options exist, which do you recommend for me and why?
Was my testing done on tissue, on a blood sample, or both?
Were other biomarkers tested, and did they affect the plan?
If my cancer stops responding to treatment, would I be tested again?
Are there clinical trials I might be eligible for?