HER2 and breast cancer

Overview

HER2 is a protein found on the surface of certain cancer cells. Some breast cancers have a lot more HER2 receptors than others. In this case, the tumour is described as being HER2-positive. 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. Women with HER2-positive breast cancer can benefit from a drug called trastuzumab (Herceptin®). Herceptin only works in people who have high levels of the HER2 protein.

Your specialist should be able to tell you if you have HER2-positive breast cancer and if Herceptin may be helpful to you.

What is HER2?

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

• Receptors are particular proteins that are present within cells or on their surface. Other proteins or chemicals 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 receptor 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.

HER2 testing

Tests can be done to find out whether a woman has HER2-positive breast cancer. Testing will usually be done at the same time as the initial biopsy or breast cancer surgery. Samples of cancer tissue from previous biopsies or an earlier surgery also may be used if you have not already been tested.

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.

Testing methods

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.

HER2 status and hormonal therapy

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.

References

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

• Martindale: The Complete Drug Reference (35th edition). Eds Sweetman et al. Pharmaceutical Press, 2006.
• Trastuzumab for the Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer. National Institute for Health and Clinical Excellence (NICE), August 2006.
• Breast Cancer (2nd Edition). Roses, D.F. Churchill Livingston, 2005.
• 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 further references, please see our general bibliography|.