ERBB2 is a gene that can change (mutate or amply). If it changes, it may help a tumour grow (oncogene). ERBB2 is more commonly known as HER2 (or HER2/neu). HER2 stands for human epidermal growth factor receptor 2.
HER2 controls a growth-promoting protein on the surface of breast cells. Each healthy cell contains 2 copies of the HER2 gene. Sometimes too many copies of the HER2 gene are present in a cell (this is called amplification), which leads to too much HER2 protein being made. This is called overexpression of HER2.
Why HER2 status testing is done
HER2 status testing is done to find out the amount of HER2 produced by a tumour. HER2 status testing can vary across Canada. It is mostly done with breast cancer tumours but may also be done with advanced stomach cancers.
HER2 status testing for breast cancer may be done:
- on the main (primary) breast tumour at the time of diagnosis
- if the breast cancer recurs or metastasizes
Research studies are showing that other types of cancer, such as ovarian, bladder and lung, may also overexpress HER2. More research is needed to determine the role that HER2 overexpression may play with these tumours. Testing for HER2 in cancers other than breast and stomach are not available in Canada outside of clinical trials.
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How HER2 status testing is done
HER2 status testing is done on a tumour sample taken with a biopsy. Testing can be also be done on stored tumour tissue. There are 3 techniques that can be used to determine HER2 status:
- Immunohistochemistry (IHC) uses special antibodies linked to a fluorescent or enzyme label to assess the amount of HER2 protein in cells.
- Fluorescent in situ hybridization (FISH) uses a special DNA probe labelled with a fluorescent dye to examine the DNA for extra copies of the HER2 gene.
- Chromogenic in situ hybridization (CISH) is sometimes used as an alternative to FISH. CISH uses a special DNA probe and an enzyme-based system, instead of a fluorescent system, to determine HER2 status. It can be used along with IHC.
A HER2 blood test is also available, but it is not a substitute for tissue testing. It may be used to monitor response to treatment in women with metastatic breast cancer who had high HER2 blood levels (greater than 15 ng/mL). Monitoring response in women with low levels of HER2 blood levels is not useful.
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What the results mean
Results of HER2 status testing are reported as:
- HER2 positive – The cancer cells are overexpressing HER2.
- HER2 negative – The cancer cells are not overexpressing HER2.
HER2-positive cancers are more aggressive and tend to grow and spread more quickly than cancers with a normal amount of HER2. They are often associated with a higher tumour grade.
HER2 overexpression usually does not change throughout the course of the disease.
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What happens if HER2 overexpression is found
If cancer cells are HER2 positive, the person may be offered treatment with a drug called trastuzumab (Herceptin). Trastuzumab is specially designed to attach to the excess HER2 proteins, and stop the growth of the cancer.
If both the IHC and the FISH tests are positive, the tumour is more likely to respond to trastuzumab. If the IHC is negative but the FISH is positive, the person with cancer may still respond to the drug.
People with HER2-negative cancer do not benefit from trastuzumab.
Currently in Canada, only breast cancer and advanced stomach cancer are treated with trastuzumab. Clinical trials are looking at the use of trastuzumab with other cancers.
For more detailed information on trastuzumab, go to sources of drug information.
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HER2 breast cancer
- About 20%–30% of invasive breast cancers overexpress HER2.
- Breast cancer cells that have BRCA1 mutations often do not overexpress HER2.
- HER2-positive breast cancers often contain lower levels of estrogen and progesterone receptors than HER2-negative tumours. Therefore, women with HER2-positive breast cancer may benefit less from certain types of hormonal therapy.
- HER2-positive tumours respond best to certain types of chemotherapy drugs, in combination with trastuzumab (Herceptin).
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HER2 stomach cancer
- About 15%–19% of advanced stomach cancers overexpress HER2.
- HER2-positive tumours respond best to certain types of chemotherapy drugs, in combination with trastuzumab.
- People with metastatic HER2-positive stomach cancer respond better to treatment with trastuzumab in combination with chemotherapy than to chemotherapy alone.
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