Breast Cancer: Biomarker Testing

Biomarker Testing for People with Breast Cancer

This section covers the following topics:

• Tumor biomarker testing for treatment selection
• Biomarker tests for prognosis in early-stage breast cancer 
• Genetic testing for inherited mutations

Biomarker testing for treatment selection

Biomarker tests look at samples of blood, tumor or other tissue for changes or abnormalities caused by cancer. These tests can give doctors clues about the cancer, including:

• how fast the cancer is growing
• which treatments are most likely to work
• whether or not the cancer is responding to treatment or growing
• whether or not the cancer has come back after remission

Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker tests used to select a specific treatment are sometimes called "companion diagnostic tests." These tests may be done on tumor tissue or (in many cases) on blood. See our Biomarker Testing section for more information. 

After breast cancer tissue is removed by surgery or biopsy, all breast cancers are tested for three common biomarkers: estrogen receptors, progesteron receptors and a protein known as HER2.

Hormone receptors: estrogen (ER) and progesterone (PR)

Testing is done to look for two separate hormone receptors, estrogen receptors (ER) and progesterone receptors (PR). 

• Cancers that test positive for estrogen and progesterone receptors are known as HR-positive. They may also be called ER/PR-positive. These cancers are often treated with hormone therapies. 
• Cancers that test negative for estrogen and progesterone receptors are known as ER/PR-negative or HR-negative. These cancers are not usually treated with hormone therapy. 

HER2 testing

HER2 is a protein that is found on all breast cancer cells. Tests measure the amount of HER2 protein in the tumor and provide a HER2 score from 0 to 3+.

• Cancers with a score of 3+ are considered HER2-positive. These cancers are often treated with drugs called "anti-HER2 agents."
• Cancers with a score of 1+ or 2+ are considered HER2-low. This is a relatively new label for breast cancer. In the past, these cancers would have been called HER2-negative or borderline. Advanced HER2-low breast cancers may be treated with the anti-HER2 agent Enhertu (T-DXd). 
• Cancers with a score of 0 are called HER2-negative. These cancers are not treated with anti-HER2 agents.

Possible HER2 scores

Triple-negative breast cancer (TNBC)

Breast cancers that are negative for the biomarkers ER, PR and HER2 are known as triple-negative breast cancers. These cancers do not usually respond to hormonal therapies or anti-HER2 targeted therapies. For this reason, TNBC is often treated with chemotherapy. New approaches to treating TNBC include immunotherapy and targeted therapies. Additional biomarker testing can help people learn if they qualify for other treatments. 

Other biomarkers used for breast cancer treatment selection

Additional biomarker testing may be done to study the genes and proteins within the cancer to help doctors choose the best treatment. Some treatments will work best for people whose cancer cells have specific changes. These treatments are sometimes called targeted therapies. The biomarker test for a specific targeted therapy is sometimes called a companion diagnostic test. Some tests look for only one biomarker at a time, while others may test for all many biomarkers at the same time. Panel tests look for multiple markers, including FDA-approved treatments as well as those that have not yet been proven effective in breast cancer. Examples of multiple biomarker tumor tests for breast cancer include:

• FoundationOne
• MSK-IMPACT
• Tempus xT

Examples of biomarkers used to guide breast cancer treatment include:

• ESR1 mutation testing in HR-positive advanced breast cancer for treatment with the drug Oserdu (olacestrant). 
• PIK3CA mutation testing in ER-positive, Her2-negative advanced breast cancer for treatment with the drug PIQRAY (alpelisib).  
• PTEN, PIK3 or AKT1 mutation testing in HR-positive, HER2-negative advanced breast cancer for treatment with the targeted therapy Truqap (capivasertib).  
• PD-L1: Testing for the PD-L1 protein can help find people with advanced triple-negative breast cancer (TNBC) who are most likely to respond to the immunotherapy drug Keytruda (pembrolizumab).
• Additional tumor biomarker testing may help people learn if they are eligible for certain clinical trials. 

Biomarker tests for prognosis in early-stage breast cancer

These tests are used for people with early-stage ER/PR-positive cancers to predict:

• if the cancer is likely to come back
• the benefit of adding chemotherapy to the treatment plan
• how long hormonal therapy should be used

Some examples of the most commonly used prognostic tests for breast cancer are listed below:

• Oncotype Dx
• Breast Cancer Index 
• MammaPrint 
• Prosigna

Genetic tests for inherited mutations for treatment selection

Genetic testing for an inherited mutation may be used to guide treatment selection for people diagnosed with breast cancer.  

• People with advanced breast cancer who test positive for an inherited BRCA1 or BRCA2 mutation may benefit from treatments known as PARP inhibitors. Two PARP inhibitors—Lynparza and Talzenna—are approved as targeted therapy for treating advanced breast cancer in people with a BRCA1 or BRCA2 mutation.
• Lynparza may be used to as adjuvant therapy after treatment for people with an inherited BRCA1 or BRCA2 mutation who have early-stage breast cancer this is high risk for recurrence. 
• People who test positive for other inherited gene mutations may qualify for clinical trials looking at targeted therapies to treat hereditary breast cancer. 

Visit our section on genetic testing for people diagnosed with breast cancer.