At a Glance
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
Test Preparation Needed?
The Test Sample
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.
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?
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.
Ask a Laboratory Scientist
Form temporarily unavailable
Due to a dramatic increase in the number of questions submitted to the volunteer laboratory scientists who respond to our users, we have had to limit the number of questions that can be submitted each day. Unfortunately, we have reached that limit today and are unable to accept your inquiry now. We understand that your questions are vital to your health and peace of mind, and recommend instead that you speak with your doctor or another healthcare professional. We apologize for this inconvenience.
This was not an easy step for us to take, as the volunteers on the response team are dedicated to the work they do and are often inspired by the help they can provide. We are actively seeking to expand our capability so that we can again accept and answer all user questions. We will accept and respond to the same limited number of questions tomorrow, but expect to resume the service, 24/7, as soon as possible.
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
(Updated July 2013). Breast Cancer Workup. Medscape reference. Available online at http://emedicine.medscape.com/article/1947145-workup#aw2aab6b5b6 through http://emedicine.medscape.com. Accessed July 2013.
Ithimakin, Suthinee et al. HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab. Cancer Research. February 2013. Available online at http://cancerres.aacrjournals.org/content/early/2013/02/14/0008-5472.CAN-12-3349.abstract through http://cancerres.aacrjournals.org. doi: 10.1158/0008-5472.CAN-12-3349 Accessed July 2013.
(Copyright 2012). Breast Cancer and Breast Pathology. John Hopkins University. Available online at http://pathology.jhu.edu/breast/biomarker-testing.php through http://pathology.jhu.edu. Accessed July 2013.
(Updated December 2012) HER2/neu Testing. Quest Diagnostics. Available online at http://www.questdiagnostics.com/testcenter/testguide.action?dc=CF_HER_2 through http://www.questdiagnostics.com. Accessed July 2013.
Markman, M. (2013 February 13, 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 2013.
Breast Cancer Management Assays. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/BreastCancer.html through http://www.arupconsult.com. Accessed July 2013.
(Updated 2013). HER2 Testing: Summary for Breast Cancer Patients. Available online at http://www.nccn.com/about-us/61-symptoms-category.html through http://www.nccn.com. Accessed July 2013.
(©2012). What to Know: ASCO's Guideline on HER2 Testing for Breast Cancer. American Society of Clinical Oncologists. Available online at http://www.cancer.net/publications-and-resources/what-know-ascos-guidelines/what-know-ascos-guideline-her2-testing-breast-cancer through http://www.cancer.net. Accessed July 2013.
(Updated June 2011). Serum HER2 Testing. Atlantic Health System. Available online at https://atlantichealth.dnadirect.com/grc/patient-site/her2-serum/index.html through https://atlantichealth.dnadirect.com. Accessed July 2013.
(November 2008) ARUP Laboratories Technical Bulleting. HER-2/neu Serum For monitoring soluble HER-2/neu protein in patients with metastatic breast cancer. Available online at http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/HER-2neu%20Serum.pdf through http://www.aruplab.com. Accessed August 2013.
Carney W, et al. Potential Clinical Utility of Serum HER-2/neu Oncoprotein Concentrations in Patients with Breast Cancer. Clinical Chemistry, October 2003 vol. 49 no. 10 1579-1598. Available online at http://www.clinchem.org/content/49/10/1579.short through http://www.clinchem.org. Accessed August 2013.
(October 2013) Wolff A, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Available online at http://www.asco.org/quality-guidelines/recommendations-human-epidermal-growth-factor-receptor-2-testing-breast-cancer through http://www.asco.org. Accessed October 2013.
Lam L, et al. Challenges in the clinical utility of the serum test for HER2 ECD. Biochim Biophys Acta. 2012 August; 1826(1): 199–208. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362659/ through http://www.ncbi.nlm.nih.gov. Accessed October 2013.
Gregory J. Tsongalis, PhD, HCLD, CC, Professor of Pathology, Director, Molecular Pathology, Dartmouth Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Check, W. (2002 February). Making the call on HER2 testing methods. CAP Today, In the News [On-line journal]. Available online at http://www.cap.org/html/publications/feature.html through http://www.cap.org.
Check, W. (2002 February). Serum HER2 testing. CAP Today, In the News [On-line journal]. Available online at http://www.cap.org/html/publications/sidebar1.html through http://www.cap.org.
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.
ACS (2001). How is Breast Cancer Diagnosed? American Cancer Society, Cancer Reference Information [On-line information]. Available online through http://www.cancer.org.
Locke, J. (2001 February). HER2/neu Testing. American Association for Clinical Chemistry, Strategies [Newsletter]. Available through AACC (http://www.aacc.org)
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)
MEDCEU (1999). Breast Cancer and HER2. MEDCEU [On-line continuing education]. Available online at http://www.medceu.com/course-no-test.cfm?CID=307 through http://www.medceu.com.
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 200-202.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 548-551.
Hicks, D. and Kulkarni, S. (2008 April 14). HER2+ Breast Cancer: Review of Biologic Relevance and Optimal Use of Diagnostic Tools. Medscape from American Journal of Clinical Pathology [On-line information]. Available online at http://www.medscape.com/viewarticle/570732 through http://www.medscape.com. Accessed July 2009.
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.
(2009 May, Updated). Breast Cancer Management Assays. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/OncologicDz/GynecologicalTumors/BreastCancerManagement.html# through http://www.arupconsult.com. Accessed July 2009.
(2008 December 02). NCCN Clinical Practice Guidelines in Oncology, Breast Cancer v.1.2009 Medscape from National Comprehensive Cancer Network [On-line information]. PDF available for download at http://misc.medscape.com/images/586/406/Breast-Medscape.pdf through http://misc.medscape.com. Accessed July 2009.
(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.