To determine whether a tumor is positive for particular HER2 (ERBB2) mutations, which helps to guide treatment and predict the course of the disease (prognosis); sometimes to monitor treatment and for cancer recurrence
When you have been diagnosed with invasive breast cancer or you had an invasive breast cancer that was treated but the tumor reoccurs or spreads (metastasizes), or when you have been diagnosed with certain types of stomach and esophagus cancer that are inoperable, locally advanced, recurrent, or metastatic
A sample of tumor tissue is obtained by doing a fine needle aspiration, needle biopsy, or surgical biopsy (a tumor removed surgically)
Before a biopsy, the physician who will obtain the sample of tumor tissue will provide instructions.
HER2 is short for the human epidermal growth factor receptor 2. (It is also known as ERBB2). In some cancers, especially breast cancer or cancers of the stomach and esophagus (gastroesophageal), the tumor cells have extra copies of the gene and excess amounts of the protein that it produces. Tumors in this category are known as HER2-positive and can be more aggressive and respond differently to treatment than HER2-negative tumors. The HER2 test performed on tumor samples determines whether a person's cancer is HER2-positive.
In normal cells, the HER2 gene codes for a protein that helps promote cell growth. When a mutation results in too many copies within a cell (amplification), HER2 then produces too much of the HER2 protein, causing HER2 to act as an oncogene, meaning that it can promote uncontrolled, cancerous growth. This happens in about one in five breast cancers and can also occur in other cancers, such as stomach and esophagus cancers.
The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) jointly recommend that the tumors of all people with invasive or recurrent breast cancer be tested for HER2. Invasive breast cancer is cancer that has spread from the ducts or lobules to other parts of the breast or to immediately adjacent tissues or organs. Similarly, ASCO and CAP recommend that patients with certain stomach and esophagus cancers (inoperable, locally advanced, recurrent or metastatic) who may also benefit from HER2-targeted therapy have their tumor tissue tested.
To determine if a tumor is positive for HER2, a sample of tumor is tested. There are two established ways to test HER2 status:
- Immunohistochemistry (IHC) measures the amount of HER2 protein present.
- Fluorescent in situ hybridization (FISH) looks at the gene level for the number of copies of the gene present; an increased number of gene copies is known as amplification.
Both IHC and FISH are acceptable testing methods for breast cancer. ASCO and CAP do not express a preference for one over the other, but if one test is equivocal (not clearly positive or negative), then the other should be done as a follow-up test for clarification of the result. For stomach and esophagus cancers, IHC is done first and FISH is reserved for follow-up clarification of equivocal IHC results.
An alternative testing method, chromogenic in situ hybridization (CISH), is also available but isn't commonly used.
- How is the test used?
After a person has been diagnosed with invasive or recurrent breast cancer, HER2 tissue testing is used to determine whether the tumor is HER2-positive. Someone with a HER2-positive tumor may benefit from HER2-targeted therapy.
Testing may also be used as a prognostic marker to help determine how aggressive the breast cancer is likely to be. It is not diagnostic but helps healthcare practitioners determine treatment options and understand more about the tumor's characteristics. Tumors that are HER2-positive tend to grow more aggressively and breast cancers with this abnormality resist endocrine (anti-hormone) therapy and some standard chemotherapies. People with HER2-positive breast cancers tend to have a poorer prognosis, but this tumor characteristic also makes them candidates to receive treatment specific for HER2-positive cancers, also known as targeted therapy.
HER2 testing is usually ordered along with estrogen and progesterone hormone receptor status tests (ER and PR). The results of these tests provide information about the person's likely prognosis and response to specific therapies, such as hormone therapy and chemotherapy.
Stomach and esophagus (gastroesophageal) tumor
For patients with inoperable, advanced, recurrent, or metastatic cancer of the stomach or esophagus who are candidates for HER2-targeted therapy, assessment of tumor HER2 overexpression is recommended to determine if trastuzumab (Herceptin) may be effective as part of their treatment.
- When is it ordered?
HER2 tissue testing is recommended along with other tests, such as estrogen and progesterone receptor status testing, as part of an initial workup of invasive breast cancer. Testing is also done when breast cancer has spread to other parts of the body (metastatic) or when a person has been successfully treated but the cancer has come back (recurrent breast cancer). In its 2015 guidelines on biomarker testing of metastatic breast cancer, ASCO recommends offering HER2 testing to everyone with accessible metastases. However, there is not enough evidence to know if changing treatment based on the test will affect an individual's outcome in this setting.
HER2 tissue testing is also recommended for patients with inoperable, advanced, recurrent, or metastatic adenocarcinoma of the stomach or esophagus who are candidates for HER2-targeted therapy.
- What does the test result mean?
HER2-positive breast cancer means the individual tested is likely to have a tumor that is aggressive, will respond poorly to endocrine treatment, and will be resistant to standard chemotherapy. The person may be considered a candidate for HER2-targeted therapy, such as trastuzumab, lapatinib or pertuzumab.
If HER2 testing is negative or equivocal by one method (IHC or FISH), then the other method is performed. If the second test is positive, the person still may benefit from HER2-targeted therapy.
If the tumor is HER2-negative, then HER2-targeted therapy isn't expected to be effective and the individual tested will avoid unnecessary side effects from treatment that is unlikely to help.
Stomach and esophagus cancers
Addition of HER2-targeted therapy in patients with HER2-positive advanced cancers of the stomach and esophagus can result in improved survival and quality of life.
If HER2 testing is equivocal or negative by IHC, then FISH may be performed. If FISH is positive, then the person still may benefit from HER2-targeted therapy.
If the tumor is HER2-negative, then adding HER2-targeted therapy is unlikely to be effective.
- Is there anything else I should know?
Sometimes, results of testing for a sample are inadequate or inconclusive. In this case, repeat testing using another sample may be necessary.
HER2 testing is not available in every laboratory. Both IHC and FISH methods require experience and special training to perform and interpret. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) have recommended guidelines for HER2 testing to ensure accuracy. Your healthcare provider may send your sample to a reference laboratory and the results may take several weeks to return.
Certain HER2-positive tumors are susceptible to treatment with HER2-targeted drugs. HER2-targeted therapy may be used alone or with some other chemotherapy agents and is typically used to treat only people who have HER2-positive tumors. If the initial HER2-targeted drug is not effective in someone with a HER2-positive tumor, then the patient may be offered another drug also designed to target HER2.
A test that measures HER2 in one's blood is also available. At present there isn't wide consensus that it is as useful for most patients; therefore it isn't routinely recommended.
- Besides HER2, what other laboratory tests may my healthcare provider order on my breast cancer tissue?
During an initial workup of invasive breast cancer, the pathologist evaluating the tumor will also test the tissue for estrogen and progesterone hormone receptor status (ER and PR). Tumors with positive estrogen and/or progesterone receptor status may have a diminished response to endocrine/hormone therapy if the tumor is also HER2-positive. Your healthcare practitioner may also order a breast cancer gene expression test to learn more about your cancer's characteristics.
- Does HER2-targeted therapy work for every tumor that is HER2-positive?
No. However, HER2-targeted therapy may be combined with other chemotherapy agents to increase effectiveness in many circumstances.
- Would this testing also be performed on a man?
Yes. Men do not get breast cancer as frequently as women, but it does occur and their cancer may also be HER2-positive. Guidelines also recommend HER2 testing for clinical decision-making in patients of any gender with advanced stomach and esophagus cancers who are potential candidates for HER2-targeted therapy.