If you have — 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. It 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 normal.

In the 1980s, researchers determined that the presence of too much HER2 protein could cause cancer to grow and spread more quickly. This discovery led to research on how to slow or alter the growth of these types of cancer cells.

These tests can determine HER2 status:

An ISH test is a type of genetic test. In an IHC test, a pathologist actually counts the number of HER2 receptors on the breast cancer cells.

The Food and Drug Administration (FDA) has approved several different ISH and IHC tests. It’s important for a doctor to test for overexpression of HER2 because the results will determine whether you’ll benefit from certain medications.

If breast cancer cells don’t have abnormal levels of HER2 proteins, the breast cancer is considered HER2-negative.

Even if your cancer is HER2-negative, it may still be estrogen-positive or progesterone-positive. Whether or not it’s hormone-positive also affects your treatment options.

In the United States, HER2-negative cases accounted for 78 percent of new female breast cancer cases between 2014 and 2018. In 7 percent of cases, the HER2 status was unknown.

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 percent of new female breast cancer cases in the United States between 2014 and 2018.

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

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 of 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 only used occasionally in HER2-negative breast cancer.

Another difference between HER2-positive treatments and HER2-negative treatments is that HER2-negative treatments are often oral medications. HER2-positive treatments are usually administered intravenously (through an IV) or by injection.

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

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

  • sacituzumab govitecan (Trodelvy), an IV treatment
  • 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)

Some of these medications are taken on their own, while others must be administered with other medications. Factors that affect your treatment regimen include whether:

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

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.

Multiple studies have shown 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 remissions.

Treatment with this medication lasts for up to 1 year. 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:

  • Herceptin biosimilars. Biosimilars aren’t 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 the newest of the HER2 drugs. It’s used to treat more advanced or metastatic breast cancer in people who have received at least 2 previous HER2 treatments.

Your HER2 status helps determine the pathology of your specific breast cancer. Your HER2 status can also help determine how aggressive the cancer is. Your doctor will use this information to evaluate your treatment options.

As of 2018, the breast cancer staging system that the American Joint Committee on Cancer (AJCC) uses now incorporates HER2 status.

Staging is complex and must take various other factors into account, 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 abnormal

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

Tumors between 2 and 5 centimeters (cm)Tumors between 2 and 5 cm
Hormone-positive Estrogen-positive and progesterone-positive
Hasn’t spread to the lymph nodes or away from the breastHas spread to 1 of 3 axillary (armpit) lymph nodes

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

If you’ve received a diagnosis of invasive breast cancer, your doctor will test for your cancer’s HER2 status. The test results will determine the best options for treating 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 continually improving.

If you receive a diagnosis of HER-positive breast cancer, learn everything you can and talk openly with your doctor about your questions.