IHC, or ImmunoHistoChemistry, is a special staining process performed on fresh or frozen breast cancer tissue removed during biopsy. IHC is used to show whether or not the cancer cells have HER2 receptors and/or hormone receptors on their surface. This information plays a critical role in treatment planning.
IHC for HER2 testing
IHC is the most commonly used test to see if a tumor has too much of the HER2 receptor protein on the surface of the cancer cells. With too many HER2 receptors, the cells receive too many signals telling it to grow and divide.
The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it’s called “HER2 negative.” If the score is 2+, it's called "borderline." A score of 3+ is called “HER2 positive.”
Research has shown that some HER2 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.
Inaccurate HER2 test results may cause women diagnosed with breast cancer to not get less than 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 medicines that work against HER2-positive breast cancers -- 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 anti-HER2 treatments -- even though the woman is unlikely to get any benefits and is exposed to the medicines' risks.
There are six medicines that work against HER2-positive breast cancer:
- Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki)
- Herceptin (chemical name: trastuzumab)
- Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine)
- Nerlynx (chemical name: neratinib)
- Perjeta (chemical name: pertuzumab)
- Tykerb (chemical name: lapatinib)
If your IHC HER2 test results are negative or borderline, you may want to ask your doctor about getting the FISH test, which uses different technology to measure HER2 status. If the FISH test results are borderline, you might want to ask your doctor if more than one pathologist reviewed the results. If the HER2 test results weren't reviewed by more than one pathologist, you may want to ask if the results can be reviewed again.
IHC test results are most reliable for fresh or frozen tissue samples. IHC tends to be an unreliable test for tissue that's preserved in wax or other chemicals.
IHC for hormone receptor testing
Most testing labs use the IHC test to see if there are hormone receptors on breast cancer cells. If hormone receptors are present, this means that the cancer cells’ growth is fueled by the hormones estrogen and/or progesterone.
Not all labs use the same method for analyzing the results of the test, and they do not have to report the results in exactly the same way. So you may see any of the following results:
- a percentage that tells you how many cells out of 100 stain positive for hormone receptors. You will see a number between 0% (none have receptors) and 100% (all have receptors)
- a number between 0 and 3. “0” means that no receptors are present, “1” a small number present, “2” a medium number, and “3” a large number
- an Allred score between 0 and 8. This scoring system is named for the doctor who developed it. The system looks at the percentage of cells that test positive for hormone receptors, as well as how well the receptors show up after staining (this is called “intensity”). This information is combined to give a score between 0 and 8. The higher the score, the more receptors were found and the easier they were to see in the sample.
- the word “positive” or “negative”
Keep in mind that a test should be done for both estrogen receptors and progesterone receptors.
If your result is reported as just the word “positive” or “negative,” ask your doctor for a more definite percentage, rating, or other number. Different labs have different cutoff points for calling the cancer either hormone-receptor-positive or hormone-receptor-negative. For example, if less than 10% of your cells stain positive (fewer than 1 in 10), one lab might call this a negative result. Another lab might consider this positive, even though it is a low test result. Research studies have shown that any positive result, no matter how low, suggests that hormonal therapy could help treat the cancer. A score of “0” is needed to completely rule out hormonal therapy as a treatment option.
Sometimes, a report will come back from the laboratory saying that the hormone status is “unknown.” This can mean one of several things:
- The test was never ordered or done.
- The sample of tissue that the laboratory received was too small to get reliable results.
- Few estrogen and progesterone receptors were present.
If there are no hormone receptors present, or they cannot be measured or seen, the cancer is called hormone-receptor-negative.
Talk with your doctor to make sure that your test is done by a laboratory with a great deal of experience in IHC testing for hormone receptors. The more tests the lab does, the more accurate your results are likely to be. If you receive a negative test result, ask for a complete explanation as to why the cancer is considered hormone-receptor-negative. You also might ask to have the test redone.
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