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. Usually this test is done on the biopsy taken for initial diagnosis and a second biopsy is not needed. 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.
No test preparation is needed.
HER-2 is an oncogene present in the nucleus of all cells. It codes 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 as well to hormonal therapy and some chemotherapy, so these patients often 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. If the ICH result is not clear, then the FISH or CISH method is often done as a follow-up test.
How is it used?
HER-2 testing is primarily used to select patients for treatment with HER-2 targeted therapy such as trastuzumab (Herceptin). Other HER-2 targeted 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. It is also used to predict the 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. It 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 there is HER-2 gene amplification in the cancer cell nucleus meaning it is producing too many copies of the HER-2 gene. If either test is positive, the patient is likely to have a more aggressive tumour. If the cancer is HER-2 positive, the patient may be treated with trastuzumab (Herceptin) or other HER-2 targeted 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 specialised therapies has increased the importance of HER-2 testing. Herceptin and other HER-2 targeted therapy may be used alone or with other chemotherapy agents. They are only useful in those who have a HER-2 positive cancer.
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 targeted therapies work for everyone who is HER-2 positive?