What to Know About HER2-Positive and HER2-Negative Breast Cancer

A diagnosis of breast cancer can be hard to take in. On top of the emotional burden it brings, this disease is complex with various types and subtypes. Learning about the specific type of breast cancer you have can help you take the next steps forward.

What are HER2-positive and HER2-negative breast cancers?

HER2 is a subtype of breast cancer linked to the human epidermal growth factor receptor 2 gene. This gene creates variants of HER2 proteins that serve as cell receptors on the outer part of breast cells. These cell receptors receive signals that direct the growth of the cells.^1,2

In some people, the HER2 gene duplicates too much. This leads to an increase in the amount of HER2 proteins produced. Too many of these HER2 proteins can result in an overgrowth of breast cells, causing tumors to form.^1,2

Breast cancers that form with large amounts of HER2 proteins present are known as HER2-positive (HER2+). Breast cancers without excess HER2 proteins are called HER2-negative (HER2-) breast cancers.^1,2

Comparing the progression and severity of HER2 subtypes

While HER2+ breast cancers are less common, they are often more severe. Only 20 percent of breast cancers are HER2+. These types of HER2+ breast cancers grow and spread more rapidly, and they also recur more often than HER2- breast cancers.^1-3

A 2018 study showed a higher risk of metastasis (spread to other parts of the body) with certain breast cancer subtypes. People with the hormone receptor (HR)+/HER2+ and HR-/HER2+ subtypes had greater rates of brain, liver, and lung metastases. Additionally, the HR+/HER2+ (versus HR+/HER2-) subtype had a higher risk of bone metastasis, as these aggressive tumors expand.⁴

How do doctors test for HER2 protein levels?

Breast cancers are often found through mammograms, ultrasounds, and biopsies of breast tissue. A bit of breast tissue taken from the body during a biopsy goes through further testing. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests can detect HER2+ and HER2- breast cancers.^1,2

IHC and FISH tests detect the amount of HER2 proteins in the breast tissue. If a certain level of these HER2 proteins is present, the breast cancer is HER2+. If not, the tumor is classified as HER2-.^1,2

Doctors usually order the IHC test first since it is more cost-effective and yields results sooner. If the IHC test results are not clear, then a FISH test is completed. The FISH test provides a more precise count of the HER2 proteins present.^1,2

The importance of early detection and retesting

The IHC and FISH tests may need to be repeated since HER2 levels can change over time. People with HER2- breast cancer can develop HER2+ tumors, and vice versa.^1,2

As with any cancer, early detection of breast cancer plays a crucial role in outcomes. The sooner you know you have HER2+ or HER2- breast cancer, the sooner you can start treatment. Finding out which of these cancers you have helps ensure you receive the right treatment.

Targeted treatments for HER2-positive breast cancer

HER2+ and HER2- breast cancers can both be treated. However, the treatments for HER2+ breast cancer differ significantly from the treatments for HER2- breast cancer.

HER2+ breast cancers are treated with HER2-targeted therapies. Monoclonal antibody drugs bind to the HER2 proteins and halt the growth of cancer cells.

Antibody-drug conjugates also join to variations of HER2 proteins and help transport chemotherapy directly to the cancer cells. Meanwhile, kinase inhibitors block the HER2 proteins from getting growth signals, preventing further replication.^1,3

Therapies and options for HER2-negative and triple-negative tumors

Chemotherapy is often used to treat breast cancers that are HER2- and do not have estrogen and progesterone hormone receptors. These are known as triple-negative breast cancers.

A limited number of other treatments may also be used to treat triple-negative tumors. These include immunotherapy, PARP inhibitors (that block certain proteins involved in cell growth and repair), radiation, and surgery.⁵

Hormone therapy can be used to treat a group of HER2- breast cancers known as triple-negative breast cancers. These tumors are HER2-, estrogen receptor-negative (ER-), and progesterone receptor-positive (PR+). Some targeted therapies can also be used to treat triple-negative breast cancers.²

Some metastatic breast cancers that are HER2- and hormone-receptor-positive can be treated with a targeted therapy called CDK4/6 inhibitors. These drugs hinder certain proteins (i.e., cyclin-dependent kinases 4 and 6) involved in the cell growth of these tumors.⁶

Looking forward: Hope through continued research

There is hope for people living with various types of HER2+ and HER2- breast cancers. Tests can help tell exactly which cancer you have, so you can begin the most effective treatment. Thanks to ongoing research, the number of treatments on hand for these breast cancers continues to increase.