HER2-positive breast cancer has unusually high levels of a protein called human epidermal growth factor receptor 2. This type of cancer grows and spreads more quickly than HER2-negative breast cancer but is not nearly as common.
If you or a loved one has received a breast cancer diagnosis, you’ve probably heard the term “HER2.” You may be wondering what it means to have HER2-negative or HER2-positive breast cancer.
“HER2” stands for “human epidermal growth factor receptor 2.” The HER2 protein was discovered in the 1980s.
HER2 proteins are found on the surface of breast cells. They’re involved in normal cell growth but can become overexpressed. This means that a person’s levels of the protein are higher than usual.
In the 1980s,
If breast cancer cells do not have abnormal levels of HER2 proteins, the breast cancer is considered HER2-negative.
Even if your cancer is HER2-negative, it may be estrogen-positive or progesterone-positive. Whether it’s hormone-positive also affects your treatment options.
In the United States,
HER2-positive breast cancers have abnormally high levels of HER2 proteins.
This can cause the cells to multiply more quickly. Excessive reproduction can result in a fast-growing breast cancer that’s more likely to spread.
HER2-positive cases accounted for
In the last 3 decades, significant progress has been made on treatment options for HER2-positive breast cancer.
HER2-low breast cancer
HER2-low breast cancer is a new classification that applies to cancer in which HER2 proteins are present, but there aren’t enough for the cancer to be considered HER2-positive. These cancers have traditionally been classified as HER2-negative.
According to the National Cancer Institute (NCI),
Treatment may include the targeted therapy fam-trastuzumab deruxtecan (Enhertu).
HER2-positive breast cancer is more rare than HER2-negative but spreads much more quickly due to the excess of HER2 protein.
HER2-positive cancers can be treated with HER2-targeting drugs, which are not effective on HER2-negative cancers.
HER2-low breast cancers are still being studied but may be treatable with certain targeted therapies.
It’s important for a doctor to test for overexpression of HER2 because the results will determine whether you’ll benefit from certain medications.
Tests that can determine HER2 status include:
- immunohistochemistry (IHC) test
- in situ hybridization (ISH) tests such as the fluorescence in situ hybridization (FISH) test
For both tests, you’ll provide a tissue sample.
In an IHC test, a pathologist actually counts the number of HER2 proteins on the breast cancer cells. The results are given a score from 0 to 3.
- A score of 0 to 1 indicates that the cancer is HER2-negative.
- A score of 2 is considered borderline, indicating the need for a FISH test to confirm whether the cancer is HER2-positive or HER2-negative.
- A score of 3 indicates that the cancer is HER2-positive.
A doctor will perform the IHC test first and then, if needed, follow up with the FISH test. A FISH test is a type of genetic test. During this test, a pathologist examines your DNA to see whether you have too many copies of the HER2 gene.
The Food and Drug Administration (FDA) has approved several types of FISH and IHC tests.
FISH tests are not as widely available as IHC tests, but they’re more accurate.
As of 2018, the breast cancer staging system from the American Joint Committee on Cancer incorporates HER2 status.
Your HER2 status can help determine how aggressive your cancer is. Your doctor will use this information to evaluate your treatment options.
Staging is complex and must account for factors such as:
- the size of the tumors
- the cancer’s hormone status
- whether the cancer has spread to nearby lymph nodes
- whether the cancer has spread beyond your breast
- whether the cancer cells look unusual
Talk with your doctor if you’d like to learn more about your cancer stage.
For more than 30 years, researchers have been studying HER2-positive breast cancer and ways to treat it.
Targeted therapies have now changed the outlook for people with stage 1, 2, and 3 breast cancers from poor to good.
While targeted therapies are part of the standard treatment for HER2-positive breast cancer, they’re used less often in HER2-negative breast cancer.
In general, your breast cancer treatment regimen will depend on the following characteristics of your cancer:
- HER2 status
- hormone receptor status
- stage
For HER2-positive breast cancers that are estrogen/progesterone receptor-positive, treatment with chemotherapy and hormone therapy may also be recommended.
Other factors that may affect your breast cancer treatment regimen include:
- whether you’ve already received hormone therapy or chemotherapy
- whether you’ve gone through menopause
- whether you have gene mutations other than HER2
Treatments for HER2-negative breast cancer
Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:
- some form of chemotherapy, depending on tumor size and lymph node involvement
- pembrolizumab (Keytruda), a biologic that is used if lymph nodes are involved or the tumor is large
- PARP inhibitors such as talazoparib (Talzenna)
Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:
- tamoxifen (Soltamox)
- abemaciclib (Verzenio)
- alpelisib (Piqray)
- olaparib (Lynparza)
- palbociclib (Ibrance)
- ribociclib (Kisqali)
Most of the medications in the previous list are taken in combination with some form of hormone treatment.
Trastuzumab (Herceptin), when used in tandem with chemotherapy, has improved the outlook for HER2-positive breast cancer. This targeted drug is often the primary treatment for the condition.
Treatments for HER2-positive breast cancer
Trastuzumab (Herceptin) is a biologic therapy that’s administered intravenously.
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Curative treatment with this medication lasts for up to 52 weeks. If you have metastatic or recurrent cancer, you may take it for much longer. Because of the risk of side effects, cardiac monitoring will continue for at least 2 years after treatment ends.
The following targeted therapies may also be used to treat HER2-positive breast cancer :
Herceptin biosimilars
Biosimilars are not exact copies of biologic drugs, but they’re reverse-engineered to produce similar effects. The FDA has approved five Herceptin biosimilars, including trastuzumab-dkst (Ogivri) and trastuzumab-qyyp (Trazimera).
Trastuzumab/hyaluronidase-oysk (Herceptin Hylecta)
The FDA approved Herceptin Hylecta in 2019. Herceptin Hylecta is an injectable medication, which means it can be administered more quickly than Herceptin. Cardiac monitoring is also required.
Pertuzumab (Perjeta)
In some cases, pertuzumab (Perjeta) may be used in conjunction with Herceptin. Doctors may recommend this for HER2-positive breast cancers at a higher risk of recurrence, such as stage 2 and above, or for cancers that have spread to the lymph nodes.
Neratinib (Nerlynx)
Neratinib (Nerlynx) may be recommended after treatment with Herceptin in cases that have a higher risk of recurrence.
Margetuximab-cmkb (Margenza)
This is one of the newest HER2 medications. It’s used to treat more advanced or metastatic breast cancer in people who have received at least two previous HER2 treatments.
Fam-trastuzumab deruxtecan (Enhertu)
This versatile medication is used as a second- or third-line treatment for non-small cell lung cancer, advanced stomach cancer, and some cases of HER2-positive breast cancer, including cases where the breast cancer cannot be removed with surgery or is metastatic.
In August 2022, the FDA also
If you’ve received a diagnosis of invasive breast cancer, a doctor will test your cancer to determine its HER2 status. The test results will help them determine which treatment options are best for your cancer.
New developments in the treatment of HER2-positive breast cancer have improved the outlook for this fast-growing type of cancer. Research is underway for new treatments, and survival rates for people with breast cancer are improving all the time.
If you receive a diagnosis of HER2-positive breast cancer, do not hesitate to talk openly with a doctor about your cancer and ask any questions that you may have.