Changes in HER2 Testing

HER2 (also called c-erbB-2) stands for human epidermal growth factor receptor-2. It is a protein on the surface of cells that can be over-expressed (too much of the protein) in approximately 20% of breast cancers. HER2 over-expression is usually associated with a worse prognosis but it also is predictive of response to certain systemic therapies.

All invasive carcinomas of the breast should be tested for HER2 over-expression. Carcinoma in situ should not be tested. There are two main ways of testing: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Both tests are acceptable and there is no consensus in the medical community as to which test is better.

The criteria for the above tests were recently changed and new guidelines were proposed by the American Society of Clinical Oncology/College of American Pathologists in 2007. These guidelines are discussed below.

HER2 by Immunohistochemistry (IHC)

IHC looks at the amount of the HER2 protein present on your cancer cells. If your cancer is tested by IHC, you will receive of a score of 0, 1+, 2+, or 3+. 0 and 1+ are considered negative (not over-expressed) and 3+ is considered positive (over-expressed). The criteria for a 3+ result have become more strict and now 30% of your carcinoma cells should show strong staining. A result of 2+ means the test was equivocal and FISH should be performed on your cancer.

HER2 by Fluorescence In Situ Hybridization (FISH)

FISH is a test that looks at your carcinoma cells to see if they have too many copies of the gene that makes HER2, also known as gene amplification. If you have FISH performed on your invasive cancer, there are three possible results: the gene is not amplified, the gene is amplified, or the result is equivocal. If you look at your report there should also be a “ratio” score given which correlates to amplified or not amplified.

Regarding FISH, the cut-off points for amplified and not-amplified have changed. The new recommendations are any ratio below 1.8 is not amplified and any ratio above 2.2 is considered amplified. The “equivocal” group refers to cancers that have a ratio between 1.8 and 2.2. In these cases, it is recommended that more cells in your cancer are counted or the test be repeated on another portion of your cancer.

Changes is Processing Your Breast Biopsy

There are new recommendations about how long your doctors should “fix” your breast tissue to get optimal test results. All biopsies are usually placed in 10% neutral buffered formalin which “fixes” the tissue so that the laboratory can then process it and make slides for the pathologist to review (click to see how pathology processes your biopsy).

The new recommendations for excisions/lumpectomies, etc. is that the tissue be placed in 10% neutral buffered formalin for a minimum of 6 hours but no more than 48 hours. Since needle core biopsies are much smaller, they may not need as much time in formalin but should not be fixed for less than one hour (the recommendation was that they be treated similar to larger specimens, at least six hours). The reason this is important is that studies have shown that the amount of time the breast tissue “fixes” can affect a positive or negative test result. Many laboratories are now putting this information into your pathology report so it is something you can easily check.

Laboratory Accreditation

The College of American Pathologists is now requiring laboratories who perform these HER2 tests to prove proficiency by showing a 95% agreement between results using their HER2 test compared to another validated test in the same laboratory or a validated test from an external laboratory. In addition, laboratories are required to participate in yearly proficiency testing to maintain accreditation.

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