Patient Test Information

_i_HER2_neu__i_

Also known as:

ERBB2; c-erbB-2; HER2 Serum

Formal name:

HER2/neu Amplification by FISH; HER2 Overexpression by IHC; HER2 Quantitative, Serum

Related tests:

Genetic Tests for Targeted Cancer Therapy, Tumor Markers, Breast Cancer Multiparameter Gene Expression Tests, Estrogen/Progesterone Receptor Status

Why Get Tested?

To determine whether a breast cancer tumor is positive for HER2/neu, which helps to guide treatment and predict the course of the disease (prognosis); sometimes to monitor treatment and for cancer recurrence

When to Get Tested?

When you have been diagnosed with invasive breast cancer

Sample Required?

A sample of breast cancer tissue obtained during a biopsy or a tumor removed surgically during a lumpectomy or mastectomy; sometimes a blood sample drawn from a vein in your arm

Test Preparation Needed?

None

How is it used?

Breast tissue testing
After a person has been diagnosed with breast cancer, HER2/neu tissue testing is used to determine whether the tumor is positive for HER2/neu and the person may benefit from treatment with trastuzumab (Herceptin®), a drug that was created to target HER2.

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/neu.

Testing may also be used as a prognostic marker to help determine how aggressive the breast cancer tumor is likely to be. It is not diagnostic but helps to determine treatment options and understand more about the tumor's characteristics.

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.

The two main ways to test HER2/neu status in tumors are:

  • Immunohistochemistry (IHC)–measures the amount of HER2 protein present and detects over-expression of the protein
  • Fluorescent in situ hybridization (FISH)–looks at the genetic level for an increase in the number of copies of the gene present, known as amplification

Both IHC and FISH are acceptable testing methods, according to the latest ASCO/CAP guidelines, but if one test is indeterminate or negative, then the other should be done as a follow-up test.

Blood testing
The blood (serum) HER2 test is sometimes used to monitor HER2/neu-positive breast cancer patients receiving cancer therapy including, for example, hormone therapy, chemotherapy, or targeted therapy. If the baseline (initial) level is elevated (greater than 15 ng/mL), then the blood test may be used to determine whether the level falls and treatment is working.

When is it ordered?

HER2/neu tissue testing is recommended along with 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).

serum HER2 testing is sometimes ordered after diagnosis to establish a baseline concentration and then, if elevated, ordered periodically to monitor cancer treatment. Occasionally, it may be ordered to help determine a cancer's HER2/neu status when there is insufficient tumor tissue available to perform tissue testing.

What does the test result mean?

Breast tissue testing
A HER2/neu test performed on breast tissue that is positive means the individual tested is likely to have a tumor that is aggressive, that will respond poorly to endocrine treatment, and will be resistant to standard chemotherapy. The person may be considered a candidate for trastuzumab (Herceptin®) therapy.

If HER2 testing is negative or indeterminate by one method (IHC or FISH), then the other method is performed. If the second test is positive, the person still may benefit from Herceptin®.

If both tests are negative, treatment with Herceptin® is not recommended. The individual tested will avoid unnecessary side-effects from treatment that is unlikely to be effective.

Sometimes, results of testing are not conclusive. In this case, retesting using another sample may be necessary.

Blood testing
Decreases in serum HER2 indicate a response to treatment; levels that stay the same or increase indicate that the treatment is not effective; concentrations that fall and then rise may indicate a cancer recurrence.

Some studies have shown that there can be differences in HER2/neu positivity between the primary tumor and tumors that have spread to other parts of the body. If someone with metastatic breast cancer is determined to be HER2/neu-negative when the primary tumor is tested but has a serum HER2 level greater than 15 ng/mL, then additional testing of tissue may be indicated.

Is there anything else I should know?

HER2/neu-positive tumors are frequently susceptible to treatment with Herceptin® (trastuzumab). Herceptin® attaches itself to excess protein molecules and inhibits the growth of the cancer. The development of this specialized therapy has increased the use of HER2/neu testing. Herceptin® may be used alone or with some other chemotherapy agents but is currently only used to treat people who have HER2/neu amplification and protein over-expression.

If Herceptin® is not effective in people with HER2 breast cancer, they may be given another drug in combination, but clinical trials are ongoing to study the effectiveness of these new therapies. 

There is emerging research that suggests Herceptin® could benefit people without HER2/neu-positive breast cancer.

HER2/neu 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 health care provider will probably send your sample to a reference laboratory and the results may take several weeks to return.

The HER2/neu gene is also amplified and its protein is over-expressed with some other cancers, such as ovarian and bladder cancer.

What is being tested?

HER2/neu is short for the human epidermal growth factor receptor 2. It is a gene that is found in healthy cells, but some people with breast cancer have tumors with excess copies of the gene and amounts of the protein it produces. Breast tumors in this category are known as HER2/neu-positive and can be more aggressive and respond differently to treatment than HER2/neu-negative tumors. The HER2/neu test performed on breast tissue determines whether a person's breast cancer is positive for HER2/neu.

In normal cells, the HER2/neu gene codes for a protein that helps promote cell growth. But when a gene mutation results in too many copies in a cell (amplification), HER2/neu then produces too much of the HER2 protein. When this happens, HER2/neu becomes an oncogene, meaning that it can promote uncontrolled, cancerous growth. This only happens in about one in five breast cancers but can also happen in other cancers, such as ovarian and bladder cancer.

Tumors that have this overexpression tend to grow more aggressively and resist endocrine (anti-hormone) therapy and some standard chemotherapies. People with HER2/neu-positive breast cancers tend to have a poorer prognosis, but this tumor characteristic also makes them candidates to receive treatment specific for HER2/neu-positive cancers, also known as targeted therapy.

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/neu.

To determine if a tumor is positive for HER2/neu, a biopsy is taken and the sample of tumor is tested. There are two main ways to test HER2/neu status:

  • Immunohistochemistry (IHC) measures the amount of HER2 protein present.
  • Fluorescent in situ hybridization (FISH) looks at the genetic level for the number of copies of the gene present, known as amplification.

Both IHC and FISH are acceptable testing methods, according to ASCO and CAP. The panel does not express a preference for one over the other. But if one test is indeterminate or negative, then the other should be done as a follow-up test.

Blood testing
Cells shed HER2 protein into the blood and a serum test is available to measure the amount of HER2 protein present in the blood of a person diagnosed with breast cancer. The serum level is loosely associated with the amount of HER2/neu-positive cancer present.

This test is not used for screening purposes and is not a substitute for tissue testing but may be ordered to help assess a person's prognosis and to monitor the effectiveness of treatment.

After an initial diagnosis of metastatic breast cancer is made, this blood test may be performed and if the initial level (baseline) is greater than 15 ng/mL, then the test may be used to monitor treatment. HER2 blood levels that remain high or drop and then increase could indicate that treatment is not working.

How is the sample collected for testing?

A sample of breast cancer tissue is obtained by doing a fine needle aspiration, needle biopsy, or surgical biopsy. For the HER2 blood test, a blood sample is drawn from a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

  1. Besides HER2/neu, what other laboratory tests may my doctor order on my breast cancer tissue?

    During an initial workup of invasive breast cancer, your doctor will likely do a tissue test for estrogen and progesterone hormone receptor status (ER and PR). Someone with a positive estrogen and/or progesterone receptor status may have a diminished response to endocrine/hormone therapy if the person is also HER2/neu-positive. Your doctor may also order a breast cancer gene expression test to learn more about your cancer's characteristics.

  2. Does Herceptin® work for everyone who is HER2/neu-positive?

    Unfortunately, it does not. Studies indicate that trastuzumab (Herceptin®) produces roughly a 50% improvement in disease-free survival and 33% improvement in overall survival. Herceptin® is often combined with other chemotherapy agents, but studies on how to make this more effective are still underway.

  3. 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/neu-positive. In addition, there are some data that HER2/neu can help determine a prognosis in prostate cancer in men.