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HER2 Testing: Summary for Breast Cancer Patients
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Based on the NCCN Task Force Report: HER2 Testing in Breast Cancer

Developed by Research Advocacy Network and NCCN

Breast cancers can be categorized as being HER2 positive or HER2 negative. HER2-positive breast cancer is faster growing and considered more aggressive. Studies1 ,2 indicate that the drug trastuzumab (Herceptin) is effective in the treatment of HER2-positive early stage breast cancer and HER2-positive metastatic breast cancer (cancer that has spread to other parts of the body). Trastuzumab is not effective in the treatment of HER2-negative breast cancers. Trastuzumab, like any drug, can have serious side effects3 and should only be given to patients likely to benefit from it. Because of the effectiveness, side effects, and cost of trastuzumab in treating HER2-positive early stage and metastatic breast cancer, it is very important to have tests that accurately determine HER2 tumor status.HER2 tumor status is used in determining a patient's treatment plan, and an incorrect test result can have serious consequences. If a HER2 test report indicates that a patient's tumor is HER2 positive when it is actually HER2 negative (false positive), the patient may be given trastuzumab, which can have serious side effects and is unlikely to be effective in treating her disease. If a HER2 test report indicates that a patient's tumor is HER2 negative when it is actually HER2 positive (false negative), her treatment plan will not include trastuzumab and the treatment may not be as effective.

The National Comprehensive Cancer Network (NCCN) convened an expert task force after reports of HER2 testing problems encountered in clinical studies involving adjuvant breast cancer therapies.4 The NCCN Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant (early stage) and metastatic setting s.


About 15 to 20% of women with breast cancer have HER2-positive tumors. The HER2 gene resides on chromosome 17 and carries the blueprint for the cell to manufacture the HER2 protein. The HER2 protein is a receptor on the surface of the cell and sends messages to the cell to grow and divide more frequently. In normal, resting (nondividing) cells, there are two copies of the HER2 gene, one on each of two copies of chromosome 17. In HER2-positive breast cancer:

*the cell has more than the normal number of copies of the HER2 gene; the gene is "amplified"

* the amount of HER2 protein in the cell increases or is overexpressed

* the increased number of HER2 receptors on the surface of the cell send more messages for the cell to grow and divide

* tumor growth can be very fast and the breast cancer is considered to be aggressive



Trastuzumab is an effective treatment for women with early stage or advanced (metastatic) HER2-positive breast cancer. Trastuzumab:

*specifically targets and binds to the HER2 receptors on the tumor cell surface

* may decrease the number of messages sent to the cell that tell it to grow and divide

* may also signal the body's immune system to destroy the cancer cell and may work with chemotherapy (e.g., paclitaxel) to destroy HER2-positive cancer cells

* is not known to be effective with HER2-negative breast cancers



There are two methods of testing for HER2 tumor status in women with breast cancer: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results from both tests are used in the clinical setting and the results of the tests influence treatment choices for women with breast cancer. The pathology laboratory where the HER2 testing is done should be accredited to perform such testing. It should have quality control procedures in place to ensure that the test is done correctly, and a quality assurance plan to validate (i.e. determine the accuracy of) the HER2 test results.

Immunohistochemistry (immuno-histo-chemistry IHC)

IHC is a protein-based test that is used to provide an assessment of the amount of HER2 protein receptors on the surface of the cancer cells. In HER2-positive tumors there is more than a normal amount of HER2 protein (i.e. HER2 protein overexpression) on the cell surface.

The IHC test is done by a pathologist in a laboratory on a sample of a tumor removed during a biopsy, a lumpectomy or a mastectomy. The steps in the procedure are:

* breast cancer tissue is prepared for testing

* the sample of tumor (a thin slice) is exposed to an antibody which attaches to the HER2 receptors

* the antibody attached to the HER2 protein receptors reacts with other substances that cause a color change in the tissue sample

* a pathologist must judge the degree of color change in the cells of the sample; the more HER2 protein the darker the staining: evaluation of the number of cells with color and the color intensity of the cells may be performed with computer imaging methods

* the percentage of cells in the sample with color and the intensity of the color of the cells on the slide determines the score for the test


The scoring for an IHC test is from 0 to 3+.

* Zero is HER2 negative

* 1+ is considered HER2 negative

* 2+ is considered a borderline or equivocal result

* 3+ is HER2 positive


Problems encountered with IHC testing:

* The protein being measured can be damaged during certain preparations of the tissue sample causing variability in test outcome.

* Evaluation of the sample often requires the pathologist to subjectively judge the degree of color (of the HER2 protein on the cell).

* False positive or false negative HER2 test results can occur


Last Updated on Thursday, 21 January 2010 10:12