New ASCO Guidelines Call for Determining HER2 Status of Every Invasive Breast Cancer

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The American Society of Clinical Oncology (ASCO) has put out new guidelines on HER2 testing for breast cancer. The new guidelines recommend that doctors do HER2 testing on every invasive breast cancer, including breast cancer that has come back (recurrent disease). The guidelines also lay out specific criteria for interpreting HER2 test results and say that HER2 testing should be done with an immunohistochemistry (IHC) or single- or dual-probe in situ hybridization (ISH) test.

The new guidelines were published online on Oct. 7, 2013 by the Journal of Clinical Oncology. Read the abstract of “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.”

ASCO is a national organization of oncologists and other cancer care providers. ASCO guidelines give doctors recommendations for treatments and testing that are supported by much credible research and experience.

Genes contain the recipes for the various proteins a cell needs to stay healthy and function normally. Some genes and the proteins they make can influence how a breast cancer behaves and how it responds to a specific treatment.

HER2 (human epidermal growth factor receptor 2) is a gene that can play a role in the development of breast cancer. The HER2 gene makes HER2 proteins. HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows and divides. But in about 25% of breast cancers, the HER2 gene doesn’t work as it should and makes too many copies of itself (called HER2 gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 proteins (HER2 protein overexpression). This makes breast cells grow and divide in an uncontrolled way. Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive in pathology reports. HER2-positive breast cancers tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers.

ASCO guidelines published in 2007 had more general criteria for determining if a cancer was HER2 positive. Since that time, new diagnostic tests have been developed that offer more detail on the percentage of cells that are overexpressing HER2 proteins or have HER2 gene amplification. The new guidelines say that if more than 10% of the cancer’s cells test positive for HER2 protein overexpression or HER2 gene amplification, the cancer is HER2-positive.

Earlier research has shown that some HER2 status test results may be wrong. This is probably because different labs have different rules for classifying positive and negative HER2 status. Each pathologist also may use slightly different criteria to decide whether the results are positive or negative. In most cases, this happens when the test results are borderline — meaning they aren't strongly HER2-positive or HER2-negative. In other cases, tissue from one area of a breast cancer can test HER2 positive and tissue from a different area of the cancer can test HER2 negative. The guidelines are trying to solve these problems by creating more specific criteria for determining if a cancer is HER2-postiive or HER2-negative.

The guidelines also recommend that:

  • Doctors request HER2 testing for every primary invasive breast cancer as well as HER2 testing for cancer at the metastatic site if it has spread beyond the breast area to other parts of the body, such as the bones or liver.
  • Doctors recommend HER2 targeted therapy treatments if the cancer is HER2-positive and don’t recommend HER2 targeted therapies for women with HER2-negative cancer.
  • Doctors shouldn’t make a decision about HER2 targeted therapy treatments until HER2 test results are confirmed as positive.
  • Pathologists should report HER2 tests results as unknown if they can’t determine whether the cancer is HER2-positive or HER2-negative.
  • Pathologists should follow a specific protocol to prepare tissue samples for testing and ensure that labs follow College of American Pathologists standards.

“The guideline is a bit more explicit about the testing methodology, and also a bit clearer about how much HER2-positive disease has to be present for a specimen to be called truly HER2-positive,” said Eric Winer, M.D., member of the Breastcancer.org Professional Advisory Board and director of breast oncology at the Susan F. Smith Center for Women’s Cancers at the Dana-Farber Cancer Institute in Boston. “This guideline states that if more than 10% of the tumor meets the criteria for HER2 positivity, then it is called HER2-positive.”

There are four HER2 tests:

  • IHC test (ImmunoHistoChemistry): The ImmunoHistoChemistry test finds out if there is too much HER2 protein in the cancer cells. The results of the IHC test can be: 0 (negative), 1+ (also negative), 2+ (borderline), or 3+ (positive — HER2 protein overexpression).
  • FISH test (Fluorescence In Situ Hybridization): The Fluorescence In Situ Hybridization test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the FISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
  • SPoT-Light HER2 CISH test (Subtraction Probe Technology Chromogenic In Situ Hybridization): The SPoT-Light test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the SPoT-Light test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
  • Inform HER2 Dual ISH test (Inform Dual In Situ Hybridization): The Inform HER2 Dual ISH test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the Inform HER2 Dual ISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).

It's important to know which HER2 status test you had. Generally, only cancers that test IHC 3+, FISH positive, SPoT-Light HER2 CISH positive, or Inform HER2 Dual ISH positive respond to the medicines that target HER2-positive breast cancers. An IHC 2+ test result is called borderline. If you have an IHC 2+ result, ask to have the tissue retested with a more precise HER2 test: the FISH test, SPoT-Light HER2 CISH test, or the Inform HER2 Dual ISH test.

Inaccurate HER2 test results may cause women diagnosed with breast cancer to not get the best care possible. If all or part of a breast cancer is HER2-positive but test results classify it as HER2-negative, doctors aren't likely to recommend HER2 targeted therapy treatments — even though the woman could potentially benefit from those medicines. If a breast cancer is HER2-negative but test results classify it as HER2-positive, doctors may recommend HER2 targeted therapy treatments — even though the woman is unlikely to get any benefits and is exposed to the medicines' risks.

If your HER2 test results are HER2-negative, you may want to ask your doctor about how confident he or she is in the lab that did the HER2 testing and if another HER2 test might make sense for your unique situation.

If your HER2 test results are borderline, it's a good idea to ask if another HER2 test makes sense for you.

For more information on HER2 testing and treatments for HER2-positive cancers, visit the Breastcancer.org HER2 Status page in the Symptoms and Diagnosis section.

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