To determine whether a cancer, usually a breast cancer, is positive for HER-2 gene amplification or protein expression, which helps to guide treatment and determine outcome. HER-2 evaluation is also used in the assessment of some other cancer types including gastric and oesophageal cancer.
A sample of cancer tissue obtained during a biopsy. Generally this test is done on the biopsy taken for initial diagnosis and a second biopsy is not necessary. While HER-2 levels can be assessed in a blood sample, this is not usually done as treatment decisions rely on testing of the cancer cells in biopsy material.
HER-2 is an oncogene present in the nucleus of all cells. It encodes for a cell surface receptor of a chemical growth factor; when the growth factor binds to the receptor it becomes activated and this causes the cell to grow. Normal epithelial cells contain two copies of the HER-2 gene and produce low levels of the HER-2 protein. In about 20-30% of invasive breast cancers (and some other cancers, such as gastric, oesophageal, ovarian and bladder cancer), the HER-2 gene has additional copies produced (gene amplification) and an abnormally large amount of the protein is produced (protein over-expression). Cancers which have this over-expression tend to grow more rapidly and do not respond well to hormonal therapy and some chemotherapy, so these patients generally have a poorer outcome.
There are two main ways to test HER-2 status in cancer tissue: immunohistochemistry (IHC) and in situ hybridization undertaken either using a fluorescent or chromogen method (FISH or CISH). IHC measures the amount of HER-2 protein present. FISH and CISH look at the level for HER-2 gene amplification (the number of copies of the gene present). IHC is currently the most widely used initial testing method; however, if the result is not clear, then the FISH or CISH method is often done as a follow-up test.
How is the sample collected for testing?
A sample of cancer tissue is obtained by doing a fine needle aspiration, needle biopsy, or surgical biopsy. HER-2 protein can be measured in a blood sample taken from a vein in the arm but it will not be raised until the tumour is large. Blood testing is not generally used for determining HER-2 status.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it used?
HER-2 testing is primarily used to select patients for treatment with HER-2 targetted therapy such as trastuzumab (Herceptin). Other HER-2 targetted therapies have also been licenced. These agents are used in the UK to treat patients with HER-2 positive early stage breast cancer, either prior to surgery and chemotherapy, or sometimes afterwards. It reduces the risk of the cancer coming back and increases the chances of cure.
Herceptin is also used for patients with advanced breast cancer that has spread elsewhere within the body or recurred after initial treatment.
HER-2 testing may also be used to help determine how aggressive a cancer is likely to be, and it is also used as a predictor of response to certain types of chemotherapy and hormone therapy.
When is it requested?
HER-2 testing is recommended as part of an initial workup of invasive breast cancer and is sometimes done with recurrent or metastatic breast cancer, or in some other cancers. It helps the doctor determine treatment options and understand more about the cancer’s characteristics.
What does the test result mean?
A positive HER-2 IHC test means that there is an excess amount of HER-2 protein on the surface of the cancer cells (the HER-2 gene product is overexpressed). A positive FISH test indicates HER-2 gene amplification in the cancer cell nucleus (production of too many copies of the HER-2 gene). If either test is positive, the patient is likely to have an aggressive tumour. HER-2 positive patients are potential candidates for therapy with trastuzumab (Herceptin) or other HER-2 targetted therapy. [See "Is there anything else I should know?"].
Is there anything else I should know?
HER-2-positive tumours may be susceptible to trastuzumab (Herceptin), and other drug therapies created to target HER-2 protein. These drugs attach to the cancer cell surface and inhibit the growth of the cancer. The development of these specialised therapies has increased the value of HER-2 testing. Herceptin and other HER-2 targetted therapy may be used alone or with other chemotherapy agents, but are only useful in those who have HER-2 amplification and protein over-expression.
HER-2 testing is not available in every pathology laboratory. IHC, FISH and CISH require experience and special training to perform and interpret. Your doctor may need to send your sample to a reference laboratory and the results may take over a week to return.
Besides HER-2, what other laboratory tests may my doctor request on my breast cancer tissue?
Do Herceptin and similar HER-2 targetted therapies work for everyone who is HER-2 positive?
Unfortunately, no. Only about one-third of patients who are positive for HER-2 will respond to HER-2 targetted therapy. There are other cellular factors involved that are not yet understood. Combination with other chemotherapy agents may make HER-2 targetted therapy more effective.