Immunohistochemistry (IHC) tests

Immunohistochemistry (IHC) tests are some of the most common tests performed on breast cancer tumor tissue. These tests help you and your doctor understand:

• What may be helping the cancer to grow
• What treatments may be most effective

IHC tests look for biomarkers—features of cancer cells that guide treatment decisions. In breast cancer, IHC tests can confirm whether the breast cancer has the following biomarkers:

• Hormone receptors: proteins that attach to estrogen and/or progesterone and tell breast cancer to grow
• HER2 receptors: proteins that signal HER2-positive breast cancer to grow

In certain cases, IHC tests may also be used to look for PD-L1 proteins, which can prevent the immune system from attacking triple-negative metastatic breast cancer cells.

Who gets IHC testing?

IHC tests are part of the standardized tests performed on:

• Tissue removed during a biopsy to diagnose any stage of breast cancer
• Tissue removed during surgery (lumpectomy or mastectomy) for early-stage breast cancer

After biopsy or surgery, a tissue sample is sent to a lab. At the lab, IHC tests check for hormone receptor status and HER2 status. Results confirm whether the cancer can be treated with hormonal therapy or HER2-targeted therapies.

Doctors may also recommend a biopsy and IHC testing in these cases:

• If metastatic breast cancer is a recurrence of an early-stage breast cancer, it’s important to know that hormone and HER2 receptor status can change over time. IHC testing can tell if the status has changed since the last diagnosis. The results can help you and your healthcare team plan the most effective treatment.
• If metastatic breast cancer is triple-negative (tests negative for hormone and HER2 receptors), IHC tests can check the cancer for PD-L1 proteins. Results can help confirm if the immunotherapy pembrolizumab (Keytruda) may be an option.

How does IHC testing work?

After doctors send tumor tissue to the lab, antibodies are added to the tissue. Antibodies are proteins typically found in the immune system. But the antibodies used in IHC tests are made in labs. These antibodies can detect specific features in cancer cells.

Each IHC test uses a unique antibody that attaches to a protein on a breast cancer cell. The antibodies are treated with a chemical that makes them change colors when the two proteins link. This is why IHC tests are sometimes called staining tests.

A specially trained doctor called a pathologist interprets the results.

How IHC test results appear on a report

In this section, we’ll talk about how IHC results may look on your pathology report. This is a report you and your doctors receive any time cancer tissue is removed and tested.

IHC test results for hormone receptor status

In most IHC testing for hormone receptor status, the cancer is considered hormone receptor-positive if at least 1% of the cells test positive for either or both hormone receptors.

There is no standard for how these results will appear in your report, but it is likely to contain some or all of this information. Your results may be reported in one of these ways:

• Positive or negative for hormone receptors (for example: estrogen positive, progesterone negative)
• The percentage of cancer cells that test positive for the hormone receptors (for example: estrogen 80%, progesterone 100%)
• A number from zero to three or the words none, weak, moderate, or strong
• An “Allred” score, which is a number between zero and nine; nine is the highest level of positivity

If your test results simply say “positive” or “negative,” it’s important to ask your doctor for a percentage. Some labs say the result is negative If hormone receptors are present in less than 10% of breast cancer cells. But hormonal therapy can still be helpful even with a low percentage of positivity.

How IHC hormone receptor-status results guide treatment decisions

If results say the cancer is hormone receptor-positive, you and your doctor will talk about treatment options including:

• Hormonal therapies
• Targeted therapies
• Chemotherapy
• Radiation therapy

Learn more about treatment for hormone receptor-positive breast cancer.

If the cancer is hormone receptor-negative, hormonal therapies and certain targeted therapies will not be effective. You and your doctor will choose treatments based on other features of the cancer, such as its HER2 status.

IHC test results for HER2 status

In IHC testing for HER2 status, results include a score from 0 to 3+ based on the volume of HER2 on the cancer cell. These scores tell you if the cancer is HER2 positive, HER2-low, or HER2 negative—or if it needs another test.

• 0: The cancer has no or almost no signs of HER2 receptors. It is HER2-negative.
• 1+: Early-stage breast cancer with a 1+ score is usually called HER2-negative. In metastatic breast cancer, doctors may consider a score of 1+ to be HER2-low. HER2-low is a score that is not yet listed on pathology reports, but may be in the future.
• 2+: A score of 2+ (sometimes called “equivocal”) is always sent for additional testing. A FISH test will confirm the true results:
  • In early-stage breast cancer, an IHC score of 2+ can be confirmed as either HER2-positive or HER2-negative with a FISH test.
  • In metastatic breast cancer:
    • An IHC score of 2+ with a positive FISH test is confirmed as HER2-positive.
    • Your doctor may consider an IHC score of 2+ with a negative FISH test to be HER2-low.
• 3+: The cancer is HER2-positive.

How IHC HER2 status results guide treatment decisions

If test results confirm the cancer is HER2-positive, HER2 targeted therapies can be effective. Other treatments may include chemotherapy and radiation therapy. Learn more about HER2-positve breast cancer.

If the breast cancer is HER2-low and metastatic, trastuzumab deruxtecan may be an option. There are also many other treatment options. Learn more about HER2-low breast cancer.

If results are HER2-negative, HER2 targeted therapies will not be effective. But there are other effective targeted therapies available. Different characteristics of the cancer, such as hormone receptor status, will help you and your doctor find the best treatment for you.

If IHC test results are negative for hormone receptors and HER2 receptors

Breast cancer that tests negative for hormone receptors and HER2 receptors is called triple-negative breast cancer. While triple-negative breast cancer can’t be treated with hormonal therapy or HER2-targeted therapy, there are other effective treatments available. These include targeted therapy and immunotherapy.

If you have metastatic, triple-negative breast cancer, talk with your doctor about your IHC test results and whether you should consider follow-up testing to find out if the cancer might actually be HER2-low. If it is, trastuzumab deruxtecan may be a treatment option.

IHC test results for PD-L1 status

If you have been diagnosed with metastatic, triple-negative breast cancer, your doctor may order an IHC test to check the levels of PD-L1 proteins. If they reach a certain level, it can keep the immune system from recognizing and attacking breast cancer cells.

These IHC test results are reported as a Combined Positive Score (CPS). This is calculated by dividing the number of PD-L1-positive breast cancer cells by the total number of breast cancer cells in the tumor tissue sample. A CPS of 10 or higher is considered positive for PD-L1.

How IHC PD-L1 test results guide treatment decisions

Metastatic, triple-negative, PD-L1-positive, breast cancer can be treated with the immunotherapy pembrolizumab (Keytruda).

No matter what your IHC test results are, there are effective treatment options available for you.