HER2 breast cancer

This page was reviewed under our medical and editorial policy by

Daniel Liu, MD, Plastic and Reconstructive Surgeon

This page was reviewed on September 20, 2022.

What does it mean to test HER2 status in breast cancer?

After a breast cancer diagnosis, the oncologist may recommend testing the tumor for HER2 protein levels. HER2 plays a role in cancer cell growth, and high levels of this protein may indicate the presence of a fast-growing tumor likely to spread. Your care team may use medicines that target HER2 to fight tumors. The American Cancer Society recommends testing all invasive breast cancer tumors for HER2 status, either with tissue from the initial biopsy or when the tumor is removed.

What is HER2?

The HER2 gene (also known as human epidermal growth factor receptor 2 or 2c-erbB-2) makes the HER2 protein on the surface of breast cells. Some breast cancers—about 20 percent—have high levels of HER2, according to the American Society of Clinical Oncology. This overexpression of HER2 happens when mutated breast cells make extra copies of, or amplify, this protein.

How do we test HER2 status?

Two tests are used to check HER2 status:

  • An immunohistochemistry (IHC) test: During an IHC test, antibodies (proteins made by the immune system) attach to the target antigen (a substance that causes the immune system to produce antibodies) on a cell. Chemicals are used to stain cells so they can be seen under a microscope. For breast cancer, the antigen is the HER2 protein.
  • Fluorescence in situ hybridization (FISH) test: The FISH test uses fluorescent dyes to highlight chromosomal changes in genes. For breast cancer, it highlights amplification of the HER2 protein.

Doctors may use one or both of these tests to diagnose breast cancer, gauge how it responds to treatment and see whether it’s recurred. IHC testing typically comes first because it’s more affordable and faster than FISH, but FISH is considered more accurate.

What do the test results mean?

Results from IHC testing for HER2 fall within three ranges:

  • 3+ (HER2-positive): Breast cancer cells overexpress HER2 proteins.
  • 0 or 1+ (HER2-negative): Breast cancer cells don’t overexpress HER2 proteins.
  • 2+ (equivocal): It’s unclear whether the breast cancer cells overexpress HER2 protein. Doctors will conduct more testing, with FISH or a different tissue sample, to try to clarify the HER2 status.

How is breast cancer categorized?

An oncology team will assign a stage to the breast cancer, from stage 1 (early) to stage 4 (advanced), based on:

  • The size of the tumor 
  • The tumor’s grade (based on how abnormal its cells appear)
  • If it’s positive for estrogen and progesterone hormone receptors (HR+) or HER2 (HER2+)
  • If the cancer cells have spread to neighboring tissue and lymph nodes 
  • If the cancer cells have metastasized (spread to distant sites in the body)

Breast cancer also falls within four HR/HER2 subtypes:

  • HR+/HER2+ (triple-positive breast cancer) means the tumor tested positive for estrogen and progesterone receptors and HER2.
  • HR-/HER2- (triple-negative breast cancer) means the tumor tested negative for estrogen and progesterone receptors and HER2. Triple-negative tumors tend to grow quickly and are often found later than other forms of breast cancer.
  • HR+/HER2- means the tumor tested positive for estrogen and progesterone receptors and negative for HER2. This subtype accounts for most cases of breast cancer.
  • HR-/HER2+ means the tumor tested negative for estrogen and progesterone receptors and positive for HER2.

According to rates from the National Cancer Institute, of 100,000 new breast cancer cases among women between 2015 and 2019:

  • 12.9 were HR+/HER2+ with a five-year relative survival rate of 90.7 percent
  • 13.2 were HR-/HER2- with a five-year relative survival rate of 77.1 percent
  • 87.4 were HR+/HER2- with a five-year relative survival rate of 94.4 percent
  • 5.2 were HR-/HER2+ with a five-year relative survival rate of 84.8 percent
  • 9.2 were of unknown status with a five-year relative survival rate of 75.5 percent

The cancer’s stage and subtype will guide treatment. For example, treatment for triple-positive breast cancer includes HER2-targeting drugs and hormone-blocking medicines.

How will HER2 status affect treatments?

Standard treatment for most breast cancer starts with surgically removing the tumor, followed by radiation therapy, chemotherapy or a combination of both. Doctors may try other drugs and approaches, such as immunotherapy, depending on the patient’s general health and the cancer’s characteristics.

For HER2-positive breast cancer, treatment may also include three kinds of targeted therapy:

  • Monoclonal antibodies are manmade antibodies that stick to HER2 receptors to slow tumor growth.
  • Antibody-drug conjugates, which are monoclonal antibodies combined with a chemotherapy drug. They deliver chemotherapy directly to cancer cells using antibodies that stick to the HER2 proteins.
  • Kinase protein inhibitors block signals from the protein. HER2 is a kinase protein.

Side effects of these treatments vary. While most are mild, there may be some serious side effects:

  • Fetal harm or death: If a patient is pregnant or plans to become pregnant, they shouldn’t take these treatments, as they may harm or kill the fetus.
  • Heart damage or heart failure: Monoclonal antibodies and antibody-drug conjugates may cause heart damage or congestive heart failure. The risk is greater if these drugs are given with chemotherapy drugs that may also hurt the heart, including Adriamycin® (doxorubicin) and Ellence® (epirubicin). A care team may test heart health before and during treatment. Damage to the heart usually improves after treatment stops.
  • Lung disease: The antibody-drug conjugate Enhertu® (fam-trastuzumab deruxtecan-nxki) may result in lung disease that may be life-threatening. A care team will carefully monitor the patient for any breathing problems.
  • Liver issues, severe diarrhea and hand-foot syndrome: The kinase inhibitors lapatinib, neratinib and tucatinib may cause liver problems and severe diarrhea. Lapatinib and tucatinib may also cause hand-foot syndrome, a painful condition in which the skin on the hands and feet turns red and may blister and peel.

What is the status of research into treatments for HER2-positive breast cancer?

Scientists continue to develop and test new drugs and treatments for HER2-positive breast cancer as first-, second- and third-line treatments.

For example, studies indicate that HR-positive tumors don’t respond as well as HR-negative tumors to most HER2-positive treatments, including kinase inhibitors. However, ongoing clinical trials suggest that the tumors respond similarly to the antibody-drug conjugate DS-8201a regardless of their HR status.

Researchers are also looking into new therapy combinations, such as combining hormone therapy with two monoclonal antibodies as a first-line treatment for patients who are not good candidates for chemotherapy. Another approach would supplement HER2-targeted therapies with immune checkpoint inhibitors and CDK4/6 and alpha-specific PI3K inhibitors. Researchers, meanwhile, are analyzing more biomarkers to better gauge the effectiveness of treatments and to predict outcomes.

Expert cancer care

is one call away.
appointments in as little as 24 hrs.