December 2006

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) asks its medical experts to develop recommendations for specific areas of cancer care. ASCO and the College of American Pathologists (CAP) issued a joint clinical practice guideline about human epidermal growth receptor 2 (HER2) testing for breast cancer. This patient guide is based on these recommendations.

As you read this guide, please keep in mind that every person treated for cancer is different. These recommendations are not meant to replace your or your doctors' judgment. The final decisions you and your doctors make will be based on your individual circumstances.

Information in ASCO's patient education materials is not intended as medical advice or as a substitute for the treating doctor's own professional judgment; nor does it imply ASCO endorsement of any product, service, or company.

HER2 is a receptor (specialized protein) on the surface of breast cells and breast cancer cells that controls cancer cell growth, invasion, and spread of the cancer to other parts of the body. Every healthy breast cell has two copies of the HER2 gene, which controls production of the HER2 protein. High levels of the HER2 gene and/or protein occur in approximately 20% of patients with breast cancer. These tumors, referred to as HER2-positive, tend to be higher risk cancers, and often respond differently to some types of treatment, such as certain types of chemotherapy or hormonal treatments.

A new class of anticancer drugs specifically blocks HER2 to stop the growth of cancer cells. One of these drugs, trastuzumab (Herceptin), is approved by the U.S. Food and Drug Administration (FDA) to treat HER2-positive breast cancer. Trastuzumab has shown to be effective against HER2-positive cancers. However, this drug is costly and causes serious side effects (especially heart weakness) in a small number of patients. Therefore, it is important to accurately determine the HER2 status of each patient’s breast cancer to make sure that the patients most likely to be helped (those with HER2-positive cancer) are offered the drug, and those unlikely to be helped (those with HER2-negative cancer) can avoid potential side effects.

The two FDA-approved methods currently used in the United States to test for HER2 are immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). IHC testing can show how much of the HER2 protein is present on the tumor cell surface, while FISH testing measures the number of copies of the HER2 gene inside each cell.

To improve the accuracy of HER2 testing, ASCO and CAP recommend the following:

• The HER2 status should be determined for each patient with invasive breast cancer.



• IHC and FISH tests are the only FDA-approved methods for HER2 testing. Either test may be used, as long as it is correctly performed, validated, and reproducible.



• The values for positive and negative test results must be clearly defined. A positive test result means that the tumor has high levels of the HER2 protein or an increased number of gene copies, while a negative test result means that the tumor does not. Test results that are not clearly positive or negative should be called "equivocal," which requires a repeat of the test and/or the use of a different test for further evaluation.



• The pathology laboratories that perform HER2 testing should follow specific testing procedures and handle tissue samples consistently.



• The pathology laboratories that perform HER2 testing are required to show 95% concordance (agreement) with another validated HER2 test for both positive and negative results, participate in ongoing internal and external quality assurance procedures, and hold current accreditation by a valid accrediting agency. (All accredited laboratories undergo an onsite inspection once every two years, participate in ongoing quality assurance activities, and have a valid Clinical Laboratory Improvement Act (CLIA) certificate or equivalent state license if the laboratory operates in New York or Washington State.

Because the results of HER2 testing make a difference in a patient's treatment and outcome, it is important that HER2 testing produces accurate results. This guideline was developed to enhance the accuracy of HER2 testing for patients with breast cancer. Use this guideline to talk with your doctor about the accuracy of your test results for HER2 in the laboratory that he or she uses.

To learn more about HER2 testing for breast cancer, consider asking your doctor the following questions:

• Which test was done on my tumor, IHC or FISH?



• What are the results of the HER2 test on my tumor sample? What do they mean?



• Is the laboratory accredited in accordance with the ASCO-CAP guidelines for HER2 testing?



• Can I obtain a copy of my pathology report?



• Is my HER2 status indicated on the pathology report?



• Based on these test results, what treatments do you recommend? Why do you believe these are the best options for this type of cancer? What are the possible side effects of these treatments?

Read the entire clinical practice guideline published in the January 1, 2007 Journal of Clinical Oncology (JCO).

Cancer.Net Guide to Breast Cancer

Cancer.Net (www.cancer.net) is the comprehensive, oncologist-approved cancer information website from ASCO. Visit Cancer.Net to find guides on more than 120 types of cancer and cancer-related syndromes, clinical trials information, coping resources, information on managing side effects, a live online chat series, medical illustrations, cancer information in Spanish, the latest cancer news, and much more. For more information about ASCO's patient information resources, call toll free 888-651-3038.

American Cancer Society
1599 Clifton Rd., NE
Atlanta, GA  30329-4251
Toll Free: 800-ACS-2345 (800-227-2345)
TTY: 866-288-4327
Phone: 404-320-3333
www.cancer.org

Breast Cancer Network of Strength
212 W Van Buren, Ste. 1000
Chicago, IL  60607
Toll Free: 800-221-2141 (English)
Toll Free: 800-986-9505 (Spanish)
Phone: 312-986-8338
www.networkofstrength.org

Breastcancer.org
111 Forrest Ave., #112
Narberth, PA  19702
www.breastcancer.org

CancerCare
275 Seventh Ave.
New York, NY  10001
Toll Free: 800-813-HOPE (800-813-4673)
Phone: 212-712-8400
www.cancercare.org

HER2 Support Group
6973 Mimosa Dr.
Carlsbad, CA  92009
Phone: 760-602-9178
www.her2support.org

National Cancer Institute
Public Inquiries Office
Building 31, Rm. 10A31
31 Center Dr., MSC 2580
Bethesda, MD  20892-2580
Toll Free: 800-4-CANCER (800-422-6237)
TTY: 800-332-8615
Phone: 301-435-3848
www.cancer.gov

Research Advocacy Network
309 E. Rand Rd., Ste. 175
Arlington Heights, IL  60004
Toll Free: 877-276-2187
www.researchadvocacy.org

The Susan G. Komen Breast Cancer Foundation
5005 LBJ Freeway, Ste. 250
Dallas, TX  75244
Toll Free: 800-IM-AWARE (800-462-9273)
Phone: 972-855-1600
www.komen.org

Young Survival Coalition
61 Broadway, Ste. 2235
New York, NY  10006
Phone: 646-257-3000
www.youngsurvival.org

About ASCO

ASCO is the world's leading professional organization representing physicians of all oncology subspecialties who care for people with cancer. ASCO's more than 20,000 members from the United States and abroad set the standard for patient care and lead the efforts to discover more effective cancer treatments, increase funding for clinical and translational research, and, ultimately, improve cancer care for the estimated 10 million people diagnosed with cancer worldwide each year. ASCO publishes the Journal of Clinical Oncology (JCO), the preeminent, peer-reviewed, medical journal on clinical cancer research, and produces Cancer.Net (www.cancer.net), a comprehensive consumer website providing oncologist-vetted cancer information to help patients and families make informed health-care decisions.

About CAP

CAP is a medical society that serves nearly 16,000 physician members and the laboratory community throughout the world. It is the world's largest association composed exclusively of pathologists and is widely considered the leader in laboratory quality assurance. The College is an advocate for high-quality and cost-effective medical care. Archives of Pathology and Laboratory Medicine, the leading peer-reviewed medical journal for pathologists worldwide, is published by the College. The College also produces MyHealthTestReminder.com, an e-mail reminder website, to help patients remember to schedule their life-saving health tests such as mammograms, Pap tests, colon cancer screenings, diabetes screenings, cholesterol testing, and to schedule their next blood donation. The site also provides preventive patient information, developed by pathologists, on these diseases. For more information, call 800-323-4040 or visit www.cap.org.

American Society of Clinical Oncology
2318 Mill Road, Ste. 800
Alexandria, VA 22314
Phone: 571-483-1300

www.asco.org
www.cancer.net
www.ascofoundation.org

© 2006 American Society of Clinical Oncology. For permissions information, contact permissions@asco.org.