This information is about HER2 testing and breast cancer. HER2 is a protein that can affect the growth of cancer cells. This information should ideally be read with our information about breast cancer and also about trastuzumab (Herceptin®). We hope that it will answer any questions you may have about HER2 testing and breast cancer.

To understand HER2, it first helps to know a little about receptors and growth factors.

Receptors are particular proteins that are present on the surface of, or within, cells. Other proteins or chemicals that circulate in the body can attach to these receptors to bring about change within a cell (for example, to make it reproduce or repair itself).

Growth factors are chemicals that attach to these receptors and stimulate cells to grow.

HER2 is a protein found on the surface of certain cancer cells. It is made by a specific gene called the HER2/neu gene. HER2 is a receptor for a particular growth factor called human epidermal growth factor, which occurs naturally in the body. When human epidermal growth factor attaches itself to HER2 receptors on breast cancer cells, it can stimulate the cells to divide and grow.

Some breast cancer cells have a lot more HER2 receptors than others. In this case, the tumour is described as being HER2-positive. It is thought that about 1 in 5 women with breast cancer will have HER2-positive tumours.

Tumours that are HER2-positive tend to grow more quickly than other types of breast cancer. Knowing if a cancer is HER2-positive can sometimes affect the choice of treatment. A drug called trastuzumab (commonly known as Herceptin®) has been developed to be effective against HER2-positive breast cancer. It is a type of monoclonal antibody. Monoclonal antibodies are treatments that can target particular proteins within the body.

Herceptin attaches to the HER2 protein, and stops human epidermal growth factor from reaching the breast cancer cells and stimulating their growth. Herceptin only works in people who have high levels of the HER2 protein.

Recent research suggests that Herceptin is useful for women with early breast cancer to help reduce the risk of the cancer coming back. It is currently known that chemotherapy and/or hormonal therapy can reduce this risk. A number of research trials looked at giving Herceptin alongside chemotherapy (comparing the results of this with those of using chemotherapy alone) to see if this further reduced the risk of cancer coming back. The results of the trials were very promising; the cancer came back in half as many women who had Herceptin combined with chemotherapy, rather than chemotherapy alone.

Herceptin was licensed in the UK for early breast cancer in 2006. The National Institute for Health and Clinical Excellence (NICE), which advises doctors on the prevention and treatment of ill-health, produced guidance on the use of Herceptin for women with HER2 positive early breast cancer in June 2006. The guidance states that Herceptin should be considered as a possible treatment after surgery and adjuvant chemotherapy (and radiotherapy, if appropriate). The guidance recommends that Herceptin is given every three weeks for one year.

Herceptin is also licensed to treat secondary breast cancer (cancer that has spread). It can be used on its own or in combination with chemotherapy.

In 2002, NICE published guidance on Herceptin® for women with secondary breast cancer and approved its use in particular circumstances.

Hormonal therapies can slow or stop the growth of breast cancer cells. They do this by:

• altering the level of particular female hormones that are produced naturally in
  the body, or
• preventing the hormones from being taken up by the cancer cells.

Hormonal therapies are most effective in women whose cancer cells have receptors for oestrogen and/or progesterone. They are referred to as being oestrogen or progesterone receptor positive. There are many different types of hormonal therapy and they all work in slightly different ways.

It has been suggested that a woman’s HER2 status might influence which hormonal therapy may be effective for her. However, more research is needed in order to reach firm conclusions.

Tests can be done to find out whether a woman has HER2-positive breast cancer. Testing can be done at the same time as initial breast cancer surgery. Samples of cancer tissue from previous biopsies, or surgery, may be used.

The two main methods used for HER2 testing are immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH):

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) can show how much of the HER2 protein is present in the tumour sample. The HER2 level is graded from 0 to 3+

• 0–1+ means that a normal amount of the HER2 protein is present and the result is HER2-negative
• 2+ means that a moderate amount of the HER2 protein is present
• 3+ means that there is a higher than normal level of HER2 protein and the result is HER2-positive.

When a tumour is scored at 2+, UK testing guidelines recommend that a further test is carried out. This is because a result of 2+ does not always mean a cancer cell has a high level of HER2. In this situation, an extra test (FISH) is used to give a definite result.

Fluorescence in-situ hybridization (FISH)

Whereas IHC measures the level of HER2 protein in the tumour sample, FISH testing measures the amount of the HER2/neu gene in each cell. This gene is responsible for the overproduction of the HER2 protein.

There is no number scale for FISH testing. The result is either:

• FISH-negative - normal levels of the gene are present, or
• FISH-positive – excessive amounts of the gene are present. This is sometimes called gene amplification.

The Department of Health announced in October 2005 that all newly diagnosed women with breast cancer will be tested for HER2. Women who have already been treated for breast cancer can be tested for HER2 if their cancer should ever come back.

If you are wondering about the relevance of HER2 testing in your situation, it may be helpful to discuss this with your specialist.

This section has been compiled using information from a number of reliable sources, including:

• Martindale: The Complete Drug Reference (33rd edition). Eds Sweetman et al. Pharmaceutical Press, 2002
• Trastuzumab for the adjuvant treatment of early-stage HER2-positive breast cancer. National Institute for Health and Clinical Excellence (NICE), August 2006.
• British National Formulary (52nd edition). British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2006
• Guidance on the use of Trastuzumab for the treatment of advanced breast cancer. National Institute for Health and Clinical Excellence (NICE), March 2002
• Diseases of the Breast (3rd edition). Eds Harris JR et al. Lippincott Williams & Wilkins, USA, 2004.
• Herceptin Plus Chemotherapy After Surgery Improves Survival of Women with Early Stage, HER2-Positive Breast Cancer. Eds Perez E et al. American Society of Clinical Oncology Annual Meeting, May 2005.

For futher references, please see general bibliography.