What is being tested?

EGFR is a short name for the epidermal growth factor receptor gene. This test detects mutations in the EGFR gene in cancer tissue. This information is useful in guiding treatment of non-small cell lung cancer.

The EGFR gene codes for a specialised protein called a receptor located on the surface of cells. Receptors recognise and bind to other substances, and the binding typically has a specific effect on the cells. EGFR is one of a group of receptors called receptor tyrosine kinases that help regulate cell growth, division, survival, and death. This regulation is a very complex process involving the activation of a series of signals along various pathways. Receptor tyrosine kinases like EGFR transmit signals from the surface of the cell to within the cell.

In normal cells, the binding of epidermal growth factor to its receptor on the cell surface is an important signal that promotes cell proliferation. Certain mutations called "activating mutations" in the EGFR gene can result in excessive signalling for growth and uncontrolled proliferation of cancer cells.

Treatment that targets EGFR is a valuable molecular approach in cancer therapy. Examples of EGFR-targeted therapy include drugs such as gefitinib and erlotinib, which are small molecules called tyrosine kinase inhibitors (TKIs) that enter cancer cells and impede signalling.

These drugs have been shown to be useful in treating non-small cell lung cancer (NSCLC). Studies have shown that targeted therapy with these TKIs will only work in a subset of NSCLC with specific activating mutations in the EGFR gene. If an activating mutation is present, as detected with an EGFR mutation test, then the drugs directed against EGFR are much more likely to be effective and the patient should benefit from targeted therapy.

How is it used?

EGFR mutation testing is used primarily to help guide treatment and determine whether someone with non-small cell lung cancer (NSCLC) may benefit from targeted therapy such as with the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. This testing detects the presence of specific activating mutations in the EGFR gene in the DNA of cells in tumour tissue.

EGFR-activating mutations can lead to uncontrolled growth of cancer cells. TKIs block the action of EGFR, which inhibits cell growth. If a person's lung cancer has an EGFR mutation, then a TKI may be effective in treating their cancer.

An EGFR mutation test may be requested by itself or as part of a series of tests that may include  ALK mutation testing. Each of these tests may be used to help determine whether a person's lung cancer will respond to targeted therapy and which type will likely be of most benefit.

When is it requested?

EGFR mutation testing is requested when an individual has been diagnosed with non-small cell lung cancer, especially adenocarcinoma, and the person is a candidate for treatment with an EGFR inhibitor.

Currently, if EGFR mutation testing is performed as part of a series of tests, then EGFR mutation testing may be done, and if that is negative, then a test for ALK mutation may be performed.
 

What does the result mean?

If EGFR mutation testing indicates that an EGFR-activating mutation is present in cancer tissue, then the affected individual is likely to respond to therapy that targets EGFR. If the tumour is negative for an EGFR mutation, then the person is not likely to respond to a tyrosine kinase inhibitor. ALK mutation testing may then be used to determine whether the person's tumour would be likely to respond to an ALK kinase inhibitor.

A person could have a negative test result if the tumour tissue sample is insufficient and/or when there are insufficient cancer cells present that contain the mutation. Additionally, there may be EGFR mutations present that are not detected by this testing.

Is there anything else I should know?

If a patient has already been exposed to a tyrosine kinase inhibitor and is showing signs of resistance to the medication, the health practitioner may order tests that look for specific EGFR resistance mutations.

In addition to non-small cell lung cancer, there is an increased amount (rather than a mutation) of EGFR present in other types of cancer. Some examples include colon cancer, glioblastoma (a type of brain cancer), and cancers of the head and neck, breast, and pancreas. This can be due to amplification and over-expression of the receptor that leads to excessive signalling for growth. Tumours that have increased EGFR protein tend to grow more aggressively, are more likely to metastasize and are more resistant to standard chemotherapies.

EGFR blocking agents (monoclonal antibodies such as cetuximab) are also routinely used for treatment of metastatic colon cancer and are used with some head and neck cancers. The use of these monoclonal antibodies do not require EGFR gene mutation testing.

The utility of EGFR inhibitors and their correlation with EGFR mutations in different types of cancers has yet to be fully established. The role of testing for certain EGFR gene mutations and the mutations' effect on a person's responsiveness to treatment continues to be explored.

EGFR mutation testing is not available in every laboratory. If a health practitioner sends a sample to a specialist reference laboratory, the results may take a few weeks before they are available.

Common questions

• Can I have my blood tested for EGFR mutations?

No. It is not the genetics of the person being evaluated but the genes of the tumour, so a sample of the tumour obtained with a biopsy is used for testing.

• What is the difference between EGFR, also known as HER-1, and HER-2/neu?

EGFR and HER-2/neu are both members of the same family of cell membrane receptors. When either EGFR or HER-2/neu is significantly increased in a cancer, it indicates a more aggressive tumour and a poorer patient prognosis. The primary differences between EGFR and HER-2/neu are that they are ordered to help evaluate different types of cancer and that the drugs that have been developed to target them are specific for that particular receptor, EGFR or HER-2/neu. HER-2/neu is used for evaluating breast cancer.

• Are there other types of testing performed to evaluate EGFR in tumours?

There is a test available that looks at the genetic level for gene amplification; it evaluates the number of copies of the gene present. Sometimes tests for EGFR gene amplification are used to determine the likely course (prognosis) of cancer of the head and neck. Tumours with amplified EGFR tend to grow more aggressively, are more likely to metastasize, and are more resistant to standard chemotherapies. People with these tumours tend to have a poorer outcome.

• Is EGFR mutation testing covered by Medicare?

Yes EGFR mutation testing may be ordered by a specialist in the investigation of non-small cell lung cancer in relation to access to erlotinib or gefitinib under the Pharmaceutical Benefits Scheme (PBS). MBS item number 73337.

More information

Cancer Australia: Lung cancer

Genetics Home Reference: How Genes Work

Rare Cancers Australia: Non-small cell lung cancer