Her-2/neu: Ask Us

At a Glance

Why Get Tested?

To determine whether a breast cancer tumor is positive for Her-2/neu, which helps to guide treatment and determine prognosis

When to Get Tested?

When you have been diagnosed with invasive breast cancer and your doctor wants to determine whether the Her-2/neu gene is being over-expressed in the tumor

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

The Test Sample

What is being tested?

Her-2/neu is an oncogene. It is a gene that codes for a protein that is a receptor for a particular growth factor that promotes cell growth. Normal epithelial cells found throughout the body contain two copies of the Her-2/neu gene and produce low levels of the Her-2/neu protein on the surface of their cells. In about 20-30% of invasive breast cancers (and some other cancers, such as ovarian and bladder cancer), the Her-2/neu gene is amplified and its protein is over-expressed. Tumors that have this over-expression tend to grow more aggressively and resist endocrine (anti-hormone) therapy and some chemotherapies. People with Her-2/neu positive breast cancers tend to have a poorer prognosis, but this tumor characteristic also makes them candidates to receive treatment specific for Her-2/neu-positive cancers.

To determine if a tumor is positive for Her-2/neu, a biopsy is taken and the sample of tumor is tested. There are two main ways to test Her-2/neu status: immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). IHC measures the amount of Her-2/neu protein present. FISH looks at the genetic level for actual gene amplification – the number of copies of the gene present. IHC is currently the most widely used initial testing method; however, if it is indeterminate or negative, then the FISH method is often done as a follow-up test.

A Her2/neu test blood test is also available. The amount of Her-2/neu protein present in the serum is loosely associated with the amount of Her-2/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 is greater than 15 ng/mL, then the test may be used to monitor treatment.

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 Her-2/neu 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.

The Test

How is it used?

After a diagnosis of metastatic breast cancer has been made, Her-2/neu testing may be used as a prognostic marker to help determine how aggressive the breast cancer tumor is likely to be. It is usually ordered along with estrogen and progesterone hormone receptor status tests (ER and PR). The results of these three tests give the doctor information about the person's likely prognosis and response to specific therapies such as hormone therapy and chemotherapy.

The serum Her2/neu test is sometimes used to monitor Her2/neu-positive breast cancer patients who are receiving cancer therapy including, for example, hormone therapy, chemotherapy, or Her-2/neu targeted therapy. If the level of serum Her-2/neu is initially elevated (greater than 15 ng/mL) then falls, it is likely that treatment is working; if it stays elevated, treatment is not working; and if the level falls then rises, the cancer may be recurring.

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When is it ordered?

Her-2/neu tissue testing is recommended along with estrogen and progesterone receptor status testing as part of an initial workup of invasive breast cancer and is sometimes performed with recurrent breast cancer. It is not diagnostic but helps the doctor determine treatment options and understand more about the tumor's characteristics.

Serum Her-2/neu is sometimes ordered initially 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 Her-2/neu status when there is insufficient tumor tissue available to perform tissue testing.

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What does the test result mean?

If an IHC Her-2/neu test is positive, it means that the Her-2/neu gene is over-expressing the Her-2/neu protein. If a FISH test is done, then amplification of the Her-2/neu gene can be detected. If either of these is positive, then the person is likely to have a tumor that is aggressive, that will respond poorly to endocrine treatment, and that will be resistant to chemotherapy. These people may be considered candidates for trastuzumab (Herceptin®) therapy, a drug that was created to target Her-2/neu protein.

If the IHC is negative but the FISH is positive, the person still may benefit from Herceptin®, but if both are negative the treatment will not be useful.

If a breast cancer is Her-2/neu-positive and the serum Her-2/neu is initially elevated, then changes in serum Her-2/neu levels can be used to help monitor the effectiveness of Herceptin treatment and detect early disease progression. Decreases indicate a response to treatment; levels that stay the same or increase indicate that the treatment is not effective; concentrations that fall, then rise may indicate a cancer recurrence. If the serum Her-2/neu is initially negative or low, such as may be seen with early cancers and with Her-2/neu-negative cancers, then it may not be useful as a monitoring tool.

Some studies have shown that there can be differences in Her-2/neu positivity between the primary tumor and tumor that has spread to other parts of the body. If a patient who has metastatic breast cancer is determined to be Her-2/neu negative when the primary tumor is tested but then has a serum Her-2/neu level greater than 15 ng/mL, then additional testing of tissue may be indicated.

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Is there anything else I should know?

Her-2/neu-positive tumors are susceptible to Herceptin® (trastuzumab). Herceptin® attaches itself to the excess protein molecules and inhibits the growth of the cancer. The development of this specialized therapy has increased the use of Her-2/neu testing. Herceptin may be used alone or with some chemotherapy agents but is only useful in those who have Her-2/neu amplification and protein over-expression.

Her-2/neu testing is not available in every laboratory. Both IHC and FISH require experience and special training to perform and interpret. Your doctor will probably send your sample to a reference laboratory and the results may take several weeks to return.

It takes a small amount of cancer tissue to perform the Her-2/neu test. If a sufficient sample is not available, your doctor may try running a serum Her-2/neu test and/or make an assumption that you are Her-2/neu-positive in order to broaden your treatment options.

The Her-2/neu gene is also amplified and its protein is over-expressed with some other cancers, such as ovarian and bladder cancer.

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Common Questions

1. Besides Her-2/neu, what other laboratory tests may my doctor be ordering on my breast cancer tissue?

During an initial workup of invasive breast cancer, your doctor will likely do a tissue test for hormone receptor status. A patient with a positive estrogen and/or progesterone receptor status may find their response to endocrine/hormone therapy diminished if they are also Her-2/neu-positive, limiting that treatment option.

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

Unfortunately, no. Only about one-third of patients who are positive for Her-2/neu will respond to Herceptin therapy. There are other cellular factors involved that are not well understood yet. Herceptin is sometimes combined with other chemotherapy agents to make it more effective.

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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 Her-2/neu-positive. In addition, there are some data that Her-2/neu can help determine a prognosis in prostate cancer in men.

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Related Pages

On This Site

Tests: Genetic Tests for Targeted Cancer Therapy
Conditions: Breast Cancer

Elsewhere On The Web

Mayo Clinic: HER2–positive breast cancer, What is it?
National Cancer Institute: What You Need to Know About Breast Cancer
Breast Cancer.org: Does the cancer have genes that are not normal?
American Cancer Society: Detailed Guide, Breast Cancer

» See all Article Sources

Article Sources

« Return to Related Pages

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

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Markman, M. (2009 June 30, Updated). Breast Cancer and HER2. Emedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1689966-overview through http://emedicine.medscape.com. Accessed July 2009.

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(2006 December). What to Know: ASCO's Guideline on HER2 Testing for Breast Cancer. American Society of Clinical Oncologists [On-line information]. Available online through http://www.cancer.net. Accessed July 2009.

Esteva, F. et. al. (2005 May 13). Clinical Utility of Serum HER2/neu in Monitoring and Prediction of Progression-Free Survival in Metastatic Breast Cancer Patients Treated With Trastuzumab-Based Therapies. Medscape from Breast Cancer Research [On-line information]. Available online at http://www.medscape.com/viewarticle/503103 through http://www.medscape.com. Accessed July 2009.

Tse, C. et. al. (2005). Evaluation of the Quantitative Analytical Methods Real-Time PCR for HER-2 Gene Quantification and ELISA of Serum HER-2 Protein and Comparison with Fluorescence in Situ Hybridization and Immunohistochemistry for Determining HER-2 Status in Breast Cancer Patients. Clinical Chemistry. 2005;51:1093-1101 [On-line information]. Available online at http://www.clinchem.org/cgi/reprint/51/7/1093 through http://www.clinchem.org. Accessed July 2009.

Zidan J, Dashkovsky I, Stayerman C, et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005 Sep 5;93(5):552-6.

Lower EE, Glass E, Blau R, Harman S. HER-2/neu expression in primary and metastatic breast cancer. 1: Breast Cancer Res Treat. 2009 Jan;113(2):301-6. Epub 2008 Feb 14.

Carney WP, Brown-Shimer S, Hamer PJ. Serum HER-2/neu testing can identify HER-2/neu positive patients previously classified as negative by tissue testing. American Association for Clinical Chemistry Annual Meeting Proceedings, 2008. Clin Chem Vol 54(56) Suppl, Pg A130: Abstract No. C-96.

Schwartz MK, et al. International Journal of Biological Markers 2000;15(4):324.

Lipton A, et al. Journal of Clinical Oncology 2002;20(6):1467.

Esteva FJ, et al. Journal of Clinical Oncology 2002;20(7):1800.

Lipton et al. Serial Serum HER2/neu Levels and Clinical Response Status for Study EGF20009 - Metastatic Breast Cancer, Sept 7th 2007, ASCO Breast Cancer Meeting, San Francisco.

Serum HER-2/neu and Relative Resistance to TRASTUZUMAB-based Therapy in Patients With Metastatic Breast Cancer. Cancer 2008; 113:1294-1301.

Sources Used in Previous Reviews

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Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

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ASCO (1996). c-erbB-2 as a Marker for Breast Cancer. American Society for Clinical Oncology [On-line guideline]. Available online at http://www.asco.org/prof/pp/html/guide/tumor/m_tumor14.htm through http://www.asco.org.

ACS (2001). Immunotherapy with Trastuzumab (Herceptin). American Cancer Society [On-line information]. Available online through http://www.cancer.org.

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Yazifi, H., and Gown, A. (2002 June). Controversies and guidelines in tissue-based HER-2/neu testing in breast cancer. Medical Laboratory Observer [Journal], Vol. 34 (6), pp 12-16,20. Available through MLO (http://www.mlo-online.com)

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