What’s the Difference Between HER2-Negative and HER2-Positive Breast Cancer?

HER2-positive breast cancer has unusually high levels of the protein human epidermal growth factor receptor 2. This type of cancer grows and spreads more quickly than HER2-negative breast cancer, but it’s not nearly as common.​

HER2-negative breast cancer HER2-positive breast cancer
does not have abnormal levels of HER2 proteins has abnormally high levels of HER2 proteins, causing the cancer to grow and spread more quickly
accounted for 78%Trusted Source of new female breast cancer cases in the United States between 2015 and 2019 accounted for 14%Trusted Source of new female breast cancer cases in the United States between 2015 and 2019
can be hormone-positive or hormone-negative can be hormone-positive or hormone-negative
less likely to be treated with targeted therapies primarily treated with the targeted therapy trastuzumab (Herceptin), but may also be treated with one or more other targeted therapies, including pertuzumab (Perjeta)
may also be treated with chemotherapy

may also be treated with chemotherapy


What HER2-positive means

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 14% of new female breast cancer cases in the United States between 2015 and 2019.

In the last 3 decades, significant progress has been made regarding treatment options for HER2-positive breast cancer.

HER2-low breast cancer

HER2-low breast cancer is a new classification that’s used to describe cancer where 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.

Around 50% to 60% of breast cancers are actually HER2-low breast cancers, according to the National Cancer Institute (NCI).

Treatment may include the targeted therapy fam-trastuzumab deruxtecan (Enhertu).

Testing for HER2

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:

For both tests, you’ll provide a tissue sample.

An ISH test is a type of genetic test. During this test, a pathologist examines your DNA to see if you have too many copies of the HER2 gene. In an IHC test, a pathologist actually counts the number of HER2 proteins on the breast cancer cells.

The Food and Drug Administration (FDA) has approved several types of ISH and IHC tests.

ISH tests are not as widely available as IHC tests, but they’re more accurate.

How HER2 affects staging

As of 2018, the breast cancer staging system that the American Joint Committee on Cancer developed now 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 take various other factors into account as well, 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 the breast
  • whether the cancer cells look unusual

For example, these two cancers are both classified as stage 1B:

HER2-negative breast cancer (stage 1B) HER2-positive breast cancer (stage 1B)
tumors between 2 and 5 centimeters (cm) tumors between 2 and 5 cm
hormone-positive estrogen-positive and progesterone-positive
has not spread to the lymph nodes or away from the breast has spread to 1 of 3 axillary (armpit) lymph nodes

Speak with your doctor if you’d like to learn more about your cancer stage.

How HER2 status affects treatment

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 your cancer’s:

  • HER2 status
  • hormone receptor status
  • stage

For HER2-positive or HER2-negative breast cancers that are estrogen-positive or progesterone-positive, treatment with hormone therapy may also be recommended.

Some people may also receive chemotherapy, depending on their cancer stage.

Other factors that may affect your breast cancer treatment regimen include whether:

  • you’ve already received hormone therapy or chemotherapy
  • you’ve gone through menopause
  • you have gene mutations other than HER2

Treatment for HER2-negative breast cancer

Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:

  • pembrolizumab (Keytruda)
  • sacituzumab govitecan (Trodelvy)
  • talazoparib (Talzenna)

Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:

  • abemaciclib (Verzenio)
  • alpelisib (Piqray)
  • everolimus (Afinitor)
  • olaparib (Lynparza)
  • palbociclib (Ibrance)
  • ribociclib (Kisqali)

Most of the medications in the previous list are taken in combination with some form of hormone treatment.

Treatments for HER2-positive breast cancer

Trastuzumab (Herceptin), when used in tandem with chemotherapy, has improved the outlook of those with HER2-positive breast cancer. This targeted drug is often the primary treatment for the condition.

Trastuzumab (Herceptin) is a biologic therapy that’s administered intravenously.

2018 literature review showed that the use of trastuzumab with chemotherapy slowed the growth of HER2-positive breast cancer better than chemotherapy alone. For some, this combination has resulted in long lasting periods of remission.

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. Cardiac monitoring will continue for at least 2 years after treatment ends, due to the risk of side effects.

Other treatments for HER2-positive breast cancer include but are not limited to these targeted therapies:

  • 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. As a result, 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. This may be recommended for HER2-positive breast cancers at a higher risk of recurrence, like 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. This includes cases where the breast cancer cannot be removed with surgery or it’s metastatic. In August 2022, the FDA also approved its use in some cases of HER2-low metastatic breast cancer.


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 inform which treatment options are best for your cancer.

New developments in the treatment of HER2-positive breast cancer have improved the outlook for people with 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.

Posted in: In Treatment, Just Diagnosed, Research, Treatment