• The genetic changes found in your breast tumor influence your outlook and help your care team recommend the most effective treatment combination.
• Breast cancer cells that are HER2-positive contain high levels of HER2, a protein that promotes cell growth.
• HER2-positive breast cancer cells tend to grow and spread quickly, but newer treatments such as targeted therapies are improving life expectancy.

Cancer begins when the genes in a cell develop certain types of changes, called mutations. Knowing which mutations your breast cancer cells carry will help you and the rest of your cancer care team understand your condition better.

About 20 percent of all breast cancer cases are HER2-positive. Most breast cancers are HER2-negative, although researchers are also recognizing a newer category, HER2-low, which is when some HER2 proteins are present on the cell’s surface but not enough to be considered HER2-positive.

HER2 status is one of many factors of breast cancer that describe important characteristics of tumors and help predict how they will grow. Your care team can more accurately forecast your prognosis (predicted outlook) and the treatments that are most likely to be successful when they are aware that your cancer is HER2-positive (also written as “HER2+”).

The HER2 Gene

Genes often have very long, specific names. The full name of the HER2 gene is human epidermal growth factor receptor 2. This is often shortened to HER2 receptor, HER2/neu, or simply HER2. It also sometimes goes by other names, such as ERBB2.

The HER2 gene makes a protein that is also called HER2. When the HER2 gene is activated (turned on), it sends signals to the cell, telling the cell to grow. The cell then prepares to divide and produce new cells.

In HER2-positive breast cancer, cell damage results in gene amplification, in which many extra copies of the HER2 gene are made (called HER2 gene overexpression). Larger numbers of HER2 genes lead cancer cells to make higher than normal levels of the HER2 protein. As a result, the cancer cells grow too quickly, forming a tumor.

In 1987, researchers funded by the National Cancer Institute (NCI) were among the first to recognize the significance of HER2 gene expression in breast cancer. They also discovered that HER2 status is linked to the risk of metastasis (cancer spreading to other areas) and recurrence (cancer returning) and can affect survival rates. It has since become an essential piece of information in breast cancer diagnosis, prognosis, and treatment.

Knowing your cancer is HER2-positive helps doctors understand why your cells are growing abnormally and provides insights about how to treat the tumor.

Is HER2 Genetic?

Cancer is a genetic disease. This means it’s a disease caused by changes in genes. In the case of cancer, there are changes in the genes that tell cells how to grow and multiply. These genetic mutations can be either acquired over time or are inherited from your parents. Most cancer is a result of acquired mutations that develop throughout life.

When a genetic mutation passes from parent to child and causes cancer, it’s called a hereditary disease. Mutations in the breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2), for example, can be inherited from either parent. Inheriting this genetic mutation does not mean someone will develop breast cancer, but it increases their risk of developing it. Because a parent can pass the genetic mutation to their child, breast cancers caused by BRCA1 or BRCA2 are both genetic and hereditary.

In the case of HER2, the mutation is not passed down from parent to child. It’s believed to develop over time as an acquired mutation and may be influenced by environment and lifestyle. So, HER2 is genetic but not hereditary.

Testing for HER2

If you are diagnosed with breast cancer, your care team will probably recommend you go through genetic testing to determine your HER2 status. This testing can be performed on your biopsy tissue or through a blood test. Genetic tests can also help your doctor see whether your cells have other cancer-related proteins, such as hormone receptors.

The first step of breast cancer diagnosis and HER2 testing is often getting a biopsy. During this procedure, doctors remove a sample of your breast tissue. The sample will then be examined by a pathologist using tests such as:

• Immunohistochemistry (IHC), which estimates the amount of HER2 protein on the outside of your cells
• Fluorescence in situ hybridization (FISH), which measures the number of HER2 genes inside your cells​

Together, these tests provide genomic information (genetic details) about your breast cancer cells and create a picture of your hormone receptor status. Read more about diagnostic tests for HER2-positive breast cancer.

Treatments for HER2-Positive Breast Cancer

Individuals with all subtypes of breast cancer may need treatments like:

• Surgery to remove the tumor and all or part of the surrounding breast
• Radiation therapy to get rid of remaining cancer cells after surgery (called adjuvant treatment) or shrink the tumor before surgery (neoadjuvant treatment)
• Chemotherapy medication to kill cancer cells throughout the body, which can be given before or after surgery
• Hormone therapy, if the tumor is also hormone receptor-positive

Most people with HER2-positive breast cancer will receive targeted therapy. These medications can find and destroy any cell that contains HER2 protein. Targeted therapy drugs attach to HER2, preventing it from sending signals to the cell to tell it to continue growing. This eventually causes the cell to die.

Clinical trials are underway to develop new anti-HER2 treatment options, both for early-stage and metastatic (cancer that has spread) breast cancer. In 2020, for example, the U.S. Food and Drug Administration (FDA) approved Phesgo, an injectable combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf, for treating early-stage or metastatic HER2-positive breast cancer.

As targeted treatments and other therapies continue to evolve thanks to cancer research, people with HER2-positive breast cancer and their cancer care team should have more and better treatment options to choose from.

If you have questions about which type of breast cancer you have or which breast cancer treatment is best for you, schedule a follow-up appointment with your oncologist.

Read more about treatments for HER2-positive breast cancer.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 69,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Do you still have questions about the genetics of HER2-positive breast cancer? Share your experience in the comments below, or start a conversation by posting on your Activities page.​