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About Breast Cancer>Testing > Biomarker testing

Biomarker testing

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A biomarker (short for biological marker) is a protein, gene mutation, or other substance that can be tested using a sample of cancer tissue or blood. Biomarker test results can help you and your doctor better understand:

  • How aggressive a breast cancer is
  • Characteristics that play a role in the cancer’s growth
  • What treatment options might be effective for that cancer


Some biomarker testing is done routinely after a breast biopsy. Other biomarker tests are done at different times before or after a breast cancer diagnosis.

Your healthcare team might use different terms for some of these tests, such as genomic testing, molecular testing, or somatic testing. Whatever terms your doctor uses, the goal is to gather information about the breast cancer to inform diagnosis, treatment planning, and follow-up.

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The importance of biomarker testing for breast cancer


Biomarker testing can be valuable in many ways. For example, it can help to:

Biomarker tests are combined with other tests to gather more information about the breast cancer. Imaging tests, such as MRI and PET scans, can help confirm whether cancer has spread beyond the breast. Biopsy can provide information about the size and behavior of the cancer. A combination of testing approaches gives a more complete picture of the breast cancer than any one test could provide alone.

You may have heard the term personalized medicine, which means using biomarkers to determine a specific treatment plan based on the unique features of the breast cancer. This is also called precision medicine.

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Types of biomarkers

In this section, we’ll walk you through breast cancer biomarkers that help with personalized treatment planning in different ways. We’ll also talk about a few less commonly known biomarkers.

Biomarker testing for those with any stage of breast cancer helps you and your doctor make treatment choices. For early-stage breast cancer, biomarker testing can check for recurrence risk and help define treatment choices. For those with advanced or metastatic breast cancer, biomarker tests can help determine treatment choices and treatment response.

Any stage | Hormone receptors

  • What they are: Proteins on the surface of cells that pick up growth signals from the hormones estrogen and/or progesterone.
  • Their function in breast cancer: When estrogen and/or progesterone are present, hormone receptors help breast cancer cells grow and multiply.
  • Biomarker test used: An immunohistochemistry (IHC) test, a type of staining technique used on tumor tissue; testing is routinely done after a biopsy. Testing can also be done if cancer recurs or metastasizes to confirm whether receptor status has changed.
  • How a positive result guides treatment: Hormone receptor-positive breast cancers can be treated with endocrine therapy, which interferes with estrogen’s ability to help the cancer grow. Examples include tamoxifen and aromatase inhibitors. In addition, hormone receptor-positive breast cancer may be eligible for treatment with certain types of targeted therapy.

Any stage | HER2 receptors

  • What they are: Proteins on the surfaces of cells that pick up growth signals from the HER2 gene.
  • Their function in breast cancer: A HER2 gene mutation in the breast cells can cause too many HER2 receptors to be created in breast cells, signaling the cells to grow and divide out of control
  • Biomarker test used: An IHC test, a fluorescence in situ hybridization (FISH) test, or both. These are different staining techniques done on a sample of cancer tissue.
  • How a positive result guides treatment: HER2-positive breast cancers can be treated with HER2-targeted therapies such as trastuzumab (Herceptin). MBC with low amounts of HER2 receptors, known as HER2-low breast cancer, may be eligible for treatment with trastuzumab-deruxtecan (Enhertu).

Learn more about HER2-positive or HER2-low breast cancer.

Early stage | Gene expression measured in genomic tests

Genomic tests such as EndoPredict, MammaPrint, OncotypeDX, and Prosigna look at the expression of groups of genes to predict the risk of recurrence in 10 years. Gene expression is a way to describe whether a gene in a cell is “turned on” or “turned off.” These genomic tests help guide decisions about whether chemotherapy is needed to reduce the risk of recurrence. The Breast Cancer Index test is another genomic test that looks at gene expression to predict the risk of hormone receptor-positive cancer recurring from five to 10 years after diagnosis. This can determine whether you are likely to benefit from continuing endocrine therapy beyond five years.

Genomic tests include any test that looks at genes inside of cancer cells. These are not the same as genetic tests for inherited mutations, which look for mutations such as BRCA1 or BRCA2 that are passed down by a family member. You can learn more about inherited mutations in the Genetics and family risk section.

Advanced or metastatic stage | AKT1 mutation

  • What it is: A gene mutation in breast cells that gives instructions for making the AKT1 protein, which helps regulate cell division, function, and survival.
  • Its function in breast cancer: The AKT1 mutation can abnormally activate the AKT1 protein, allowing cells to grow and divide without control.
  • Biomarker test used: A test such as FoundationOne CDX that uses next-generation sequencing technology to look for gene mutations in cancer cells. NGS can be used on tumor tissue or a blood sample. These tests can search hundreds of genes at the same time for mutations and alterations.
  • How a positive result guides treatment choices: Breast cancer that is hormone receptor-positive, HER2-negative, and tests positive for an AKT1 mutation can be treated with capivasertib (Truqap) along with the endocrine therapy fulvestrant.

Advanced or metastatic stage | ESR1 mutation

  • What it is: A mutation in the estrogen-receptor 1 gene, abbreviated as ESR1. The ESR1 gene carries instructions for building estrogen receptors on the surface of cells.
  • Its function in breast cancer: In people with hormone receptor-positive, HER2-negative breast cancers, an ESR1 mutation indicates the cancer is no longer as responsive to endocrine therapy, especially aromatase inhibitors. This mutation changes the shape of the estrogen receptors. As a result, the receptors become activated, like an “on” switch that stays on, and tell the cancer cells to keep growing.
  • Biomarker test used: A test that uses NGS, such as Guardant 360 CDx or FoundationOne CDx. These tests search for multiple gene mutations at the same time.
  • How a positive result guides treatment choices: The cancer may be eligible for treatment with elacestrant (Orserdu), a newer form of endocrine therapy, depending on what treatments a person had in the past.

Learn more about ESR1 mutation testing.

Advanced or metastatic stage | PD-L1 protein expression

  • What it is: PD-L1 is a protein found on healthy cells that prevents cells in the immune system, called T cells, from attacking them.
  • Its function in breast cancer: If cancer cells have too much PD-L1 on their surface, they can turn the body’s T cells off so that they won’t attack the cancer. This allows breast cancer to grow unchecked.
  • Biomarker test used: An IHC test uses a sample of cancer tissue to measure the amount of PD-L1 present.
  • How a positive result guides treatment choices: In metastatic, triple-negative breast cancer (which tests negative for hormone receptors and HER2 receptors), a positive PD-L1 result means the cancer can be treated with pembrolizumab (Keytruda), an immunotherapy that blocks PD-L1 to help the body’s own immune system to attack cancer cells.

Advanced or metastatic stage | PIK3CA mutation

  • What it is: A mutation in the PIK3CA gene that makes one of the proteins in an enzyme called PI3K, which is important in many cell functions.
  • Its function in breast cancer: In MBC cells, a PIK3CA mutation can cause PI3K to become too active, allowing cancer cells to grow and thrive.
  • Biomarker test used: A test that uses NGS technology, such as FoundationOne CDx, can look for PIK3CA mutations using a tissue or blood sample.
  • How a positive result guides treatment: MBC that is hormone receptor-positive, HER2-negative, and PIK3CA mutation-positive can be treated with the targeted therapy alpelisib (Piqray) along with the endocrine therapy fulvestrant. Another option is capivasertib plus fulvestrant.

Advanced or metastatic stage | PTEN alteration

  • What it is: An alteration in the PTEN gene, which provides instructions for making an enzyme that keeps cells from dividing and growing out of control.
  • Its function in breast cancer: Alterations in the PTEN gene can cause uncontrolled cell growth and division, leading to the development of breast cancer. In some cases, the mutation is inherited from a parent, but more commonly, it develops in breast cells.
  • Biomarker test used: A test that uses NGS technology on blood or tumor tissue, such as FoundationOne CDx or Guardant 360 CDx.
  • How a positive result guides treatment: MBC that is hormone receptor-positive, HER2-negative, and PTEN-alteration positive can be treated with capivasertib plus fulvestrant. Capivasertib interrupts the activity of PTEN.

Metastatic stage | NTRK gene fusion

  • What it is: A mutation that happens when the NTRK gene fuses, or joins with, a gene on another chromosome.
  • Its function in breast cancer: NTRK gene fusion can produce abnormal proteins that may cause cancer cells to grow.
  • Biomarker test used: FISH tests and tests that use NGS technology, such as FoundationOne CDx and Guardant 360.
  • How a positive result guides treatment: Locally advanced breast cancer or MBC testing positive for NTRK gene fusion may be eligible for treatment with larotrectinib (Vitrakvi), or entrectinib (Rozlytrek), targeted therapies that block the abnormal proteins from helping cancer cells grow.

Advanced or metastatic stage | MSI-H

  • What it is: MSI-H stands for “microsatellite instability-high,” which means that breast cancer cells have a high number of mutations in short, repeated sequences of DNA (known as microsatellites).
  • Its function in breast cancer: MSI-H breast cancer cells may be less able to correct DNA mistakes. This is sometimes called mismatch repair deficient (dMMR).
  • Biomarker tests used: IHC tests, tests that use NGS technology such as FoundationOne CDx, or PCR (polymerase chain reaction) tests, which use a sample of blood, cancer tissue, or saliva to look for specific gene changes.
  • How a positive result guides treatment: MSI-H breast cancer may be eligible for treatment with immunotherapies such as pembrolizumab or dostarlimab (Jemperli).

Advanced or metastatic stage | TMB-High

  • What it is: TMB stands for tumor mutational burden. It is a measure of how many mutations are in the DNA of cancer cells.
  • Its function in breast cancer: High TMB appears to be associated with higher production of abnormal tumor proteins. This means that immunotherapy may be more likely to be effective.
  • Biomarker test used: A somatic mutation test, such as FoundationOne CDx, that uses NGS technology on tumor tissue or a blood sample to look at hundreds of genes at once.
  • How a positive result guides treatment: TMB-High breast cancer may be eligible for treatment with the immunotherapy pembrolizumab.

Advanced or metastatic stage | RET fusion

  • What it is: RET fusion happens in cancer cells when the DNA of a gene called RET fuses with a different gene. This activates an enzyme that tells cells to keep growing, leading to tumor formation.
  • Its function in breast cancer: RET fusion can drive uncontrolled cell growth.
  • Biomarker test used: A test that uses NGS technology on tumor tissue or a blood sample, such as FoundationOne CDx. NGS looks at hundreds of genes at once.
  • How a positive result guides treatment: MBC with RET fusion may be eligible for treatment with selpercatinib (Retevmo), which targets the enzyme that causes the cancer cells to grow.

Advanced or metastatic stage | Cancer antigens

Cancer antigens are proteins or other molecules found on the surface of cancer cells, but not normal cells. In MBC, if certain antigen levels are elevated at the time of diagnosis, they may be used to follow the response to treatment. These tests also may be useful if your doctor suspects metastases to the bones or liver.

If the antigen level increases over time, your doctor may decide to switch therapies or monitor you more closely. However, the tests aren’t perfect, because antigen levels can be elevated for other reasons besides cancer. Examples of antigens include:

  • CA 15-3: These biomarkers may be used to monitor MBC during treatment.
  • CA 27-29: These biomarkers also may be used to monitor MBC during treatment.
  • CEA: CEA stands for carcinoembryonic antigen. High levels may indicate that breast cancer has spread to other parts of the body. Testing for CEA can also help doctors monitor how the cancer is responding to treatment.

Advanced or metastatic stage | Circulating tumor cells (CTC)

Circulating tumor cells are cancer cells that have broken away from a tumor and entered the blood. CTC blood tests can be used to look for early signs of recurrence and monitor response to treatment. Tests such as CellSearch can detect CTCs in the blood.

Learn more on the Blood tests page.

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Types of biomarker tests


In this section, you can learn more about the biomarker tests mentioned above.

Cancer antigen blood tests


Cancer antigen tests look for certain proteins in the blood that can be elevated in the presence of breast cancer. Examples include CA 15-3, CA 27-29, and carcinoembryonic antigen (CEA). Antigen tests can measure response to treatment and whether the cancer is growing or spreading.

Circulating tumor cell (CTC) tests

CTC tests, such as CellSearch, are blood tests that look for cancer cells that were shed from a tumor and are circulating through the bloodstream. Learn more on the Blood tests page.

Circulating tumor DNA (ctDNA) tests

ctDNA tests analyze a blood sample to look for fragments of genetic information shed by cancer cells into the bloodstream. In MBC, ctDNA tests can be used to look for mutations in genes such as AKT1, ESR1, and PIK3CA that can help match a cancer to a targeted therapy. ctDNA tests are also being studied in the detection of minimal residual disease—tiny amounts of cancer that don’t show up on imaging tests. ctDNA testing is sometimes called liquid biopsy. Learn more about ctDNA testing.

Genomic tests for gene expression

Gene expression is a measure of whether a gene is “turned on” or “turned off” in a cell. Genomic tests, also called genomic assays, look at the expression of groups of genes in tumor tissue to determine how likely early-stage breast cancer is to recur within five or 10 years, and whether it would be helpful to undergo chemotherapy and/or continue endocrine therapy beyond five years.

While genomic tests look at gene activity in cancer cells, tests for inherited genetic mutations look for gene abnormalities passed down from a parent. Inherited mutations include BRCA1 and BRCA2. Visit the Genetics and family risk section to learn more.

Immunohistochemistry (IHC) tests

IHC tests are done on a sample of the cancer tissue removed during a biopsy or surgery. They use immune proteins called antibodies, which attach to antigens, substances on the surface of a cell. These antibodies are made in the lab, and chemicals are added to them so they change color if they find a specific antigen. This is why an IHC test is sometimes referred to as a staining assay. IHC tests can be used to test for several biomarkers that can help with treatment choices, including:

Fluorescence in situ hybridization (FISH)


FISH tests are done on a sample of the tumor tissue to find out if breast cancer is HER2-positive or HER2-low. These tests use a fluorescent dye to look for extra copies of HER2 genes in cancer cells. FISH testing is often done in combination with IHC testing. A HER2-positive result means that the cancer is eligible for HER2-targeted therapies.

Next-generation sequencing (NGS)

NGS is a technology used in somatic mutation testing, which looks for gene mutations in tumor tissue or blood. NGS is sometimes called broad molecular profiling. These tests find hundreds of mutations or alterations that may be present in a tumor’s genes. They can be used in locally advanced breast cancer or MBC to find out if the cancer can be matched to a targeted therapy.

Examples of tests that use NGS include FoundationOne CDx and Caris Life Sciences molecular profiling. Many large academic medical centers have developed their own molecular profiling tests.

NGS is now used regularly in MBC. Usually, it is used if MBC progresses after a first-line treatment. Testing at this time can help with decision-making about what treatment to try next. In some situations, NGS is used when MBC is first diagnosed. If you have been diagnosed with MBC, talk with your doctor about what’s best for your situation.

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Challenges and limitations


Like all medical tests, biomarker testing can have limitations. Here are some examples:

Testing positive for a biomarker doesn’t always mean that a targeted therapy will be effective. Many biomarkers are used to decide whether a person is likely to benefit from a certain treatment. However, having the biomarker doesn’t guarantee the cancer will respond to the treatment.

Testing for different biomarkers may require more than one tissue sample. In MBC, for example, your doctor might need to biopsy (remove) tissue from metastases in different areas of the body. Or, the first biopsy might not yield enough usable tissue for testing, which means another biopsy would need to be done.

Many biomarker tests and targeted therapies are still being researched, so they may not be easily available. Your insurance plan might not cover every type of biomarker testing. In addition, testing positive for a specific biomarker could match you to a therapy that is only available through a clinical trial. If the trial is full or not enrolling people in your area, you may not be able to participate. Still, it’s always a good idea to ask about clinical trials. You can ask about trials no matter where you are in diagnosis or treatment.

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Clinical trials and biomarkers


All the biomarkers used in breast cancer diagnosis and treatment first had to be tested in clinical trials. More are being studied now. That’s why it’s so important to consider participating in clinical trials.

Biomarkers are a major area of focus for breast cancer clinical trials. Many new biomarkers are being investigated, and research is also being done to find new and improved treatments for familiar biomarkers. One example: New immunotherapies that can target HER2-positive breast cancers.

You can learn more about the benefits of participating in biomarker testing and treatment research on the Clinical trials page and the Metastatic trial search page.

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Paying for biomarker testing

Biomarker testing allows your healthcare team to tailor treatment to your unique diagnosis—choosing only those treatments that are likely to be helpful. Still, not all of these tests are routinely covered by health insurance.

Biomarker tests that are well-established in breast cancer care are usually covered by insurance. Examples include:

  • IHC testing for hormone receptors and HER2 receptors
  • FISH testing for HER2 receptors
  • Genomic tests such as OncotypeDX for predicting risk of recurrence and benefit of chemotherapy in early-stage breast cancer


Tests and testing technologies that are still being studied, such as NGS, circulating tumor cell testing, and ctDNA tests, might not be covered. In the case of NGS, if the test is FDA-approved for use in locally advanced breast cancer or MBC, it may be more likely to be covered. Medicare and Medicaid cover NGS tests used in this situation.

Depending on your health insurance plan, your doctor might need to provide evidence that a test is necessary to guide treatment decisions. Another option is to ask your doctor about participating in a clinical trial that includes a biomarker test you need.

For more information about paying for care, visit Financial assistance.

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FAQ

Here are answers to frequently asked questions about biomarker testing:

What is biomarker testing for breast cancer treatment?

Biomarker testing is testing for hormone receptors, HER2 receptors, gene expression, genetic mutations, proteins, or other substances that can be found in the cancer tissue or in the blood. These tests can provide more information about the biology of the cancer: what’s driving the cancer’s growth, how likely it is for early-stage breast cancer to come back, or whether MBC is progressing. This information helps guide treatment choices.

How do biomarkers influence breast cancer treatment?

Doctors can use biomarker test results to select specific treatments that are more likely to be effective against the cancer. These results also can be helpful in predicting the risk of recurrence, and how likely the cancer is to grow and spread. A higher-risk breast cancer may require closer follow-up.

Can biomarker testing predict treatment side effects?

No, biomarker testing cannot predict treatment side effects. However, it can often be helpful in selecting targeted therapies, which often have less intense side effects than chemotherapy.

What are common biomarkers for breast cancer?

The most common biomarkers tested for in breast cancer are:

These tests are done after every breast cancer diagnosis and can also be done again later, after lumpectomy, mastectomy, or if cancer recurs or metastasizes. Other common breast cancer biomarkers include:

  • Gene expression in early-stage, hormone receptor-positive tumor tissue seen in genomic tests such as Oncotype DX and MammaPrint; looking at certain groups of genes to learn whether they are “turned on” or “turned off” can determine the likelihood of recurrence and whether chemotherapy is likely to be beneficial
  • Gene mutations in locally advanced breast cancer or MBC tissue, such as mutations in ESR1, PIK3CA, or AKT1 genes, which can help match specific breast cancers with specific endocrine or targeted therapies
  • PD-L1 proteins on MBC cells, which can help match specific breast cancers with immunotherapies
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Reviewed and updated: April 15, 2024

Reviewed by: Pallav K. Mehta, MD

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