Tests for metastatic breast cancer

Metastatic breast cancer (MBC) can develop in people who previously had early-stage breast cancer either shortly after initial diagnosis, or years—even decades—afterwards. Less commonly, it can be a first-time breast cancer diagnosis (de novo MBC).

Signs could include:

• A lump that you feel in the breast or other areas of the body, such as lymph nodes or skin
• Pain in the bones or joints
• Headache
• Shortness of breath
• Abdominal pain or bloating

Tests to diagnose MBC can include a physical exam, imaging tests, blood tests, and biopsy. Your doctor might recommend these tests if you’re having symptoms that suggest MBC, or if early breast cancer follow-up testing such as blood work or routine imaging studies show signs of a recurrence.

If a diagnosis confirms MBC, other tests can help you and your healthcare team:

• Learn more about the cancer
• Match specific cancer characteristics to effective treatments
• Monitor the cancer’s response to treatment

Your doctor will look at your individual medical history when deciding which tests might be helpful. If the breast cancer is a recurrence, your care team will work with you and your current and past care team members to gather previous pathology reports and biomarker test results that will inform the treatment plan going forward.

At LBBC, we know that having any kind of breast cancer test can trigger intense feelings such as anxiety, anger, or sadness. If this is where you are now, know that you’re not alone—and we have many emotional health and support resources available for you.

Below, we’ll explain more about tests that can confirm diagnosis and help you and your team find the best treatment plan for you.

Tests that may indicate MBC is present

After you have a physical exam, your doctor may recommend some of the following tests to look for signs of MBC. Your doctor will look at your unique medical history and any symptoms to determine which tests may be most helpful.

Blood tests

Here are some of the common blood tests that suggest MBC could be present:

• Blood chemistry tests measure special proteins, called enzymes, in the blood. If levels aren’t normal, it may mean that cancer has spread. These tests can also assess whether the liver and kidneys are functioning normally. Learn more on the Blood tests page.
• Cancer antigen tests look for tumor proteins in the blood. Sometimes, but not always, the presence of these proteins can indicate breast cancer spread. Common breast cancer antigens include CA 15-3, CA 27.29, CA-125, and CEA. Learn more about cancer antigens on the Biomarker testing page.
• Circulating tumor cell (CTC) tests look for cancer cells in the blood that have broken away from a tumor. CTC tests are generally not routinely done to establish diagnosis of MBC because they are not reliable enough for this purpose, but are sometimes used to monitor disease or for research purposes. Learn more on the Blood tests page.
• Complete blood count (CBC) tests measure red and white blood cell counts and assess whether cancer might have spread to the bone marrow. Learn more on the Blood tests page.
• Circulating tumor DNA (ctDNA) tests check the blood for minimal residual disease—microscopic amounts of cancer that are too tiny to show up on imaging tests—to learn more about whether early-stage cancer may have recurred. ctDNA tests are sometimes called liquid biopsy. These tests are still very early in development and guidelines on how to use them have not yet been established. Learn more about ctDNA testing.

Imaging tests

Here are some of the common imaging tests used to check for possible MBC:

• Bone scans use radioactive tracer to look inside of bones for signs of breast cancer metastasis. Read more about Bone scans.
• Chest x-rays can check to see if breast cancer may have spread to the lungs. Visit the chest x-ray page to learn more.
• Computed tomography (CAT or CT) scans take pictures of the inside of the body. CT scans can look for signs of cancer that has spread from the breast to other parts of the body, such as the lymph nodes, bones, lungs, liver, or brain. Learn more about CAT scans.
• Magnetic resonance imaging (MRI) can measure the size of a tumor and can also be used to check for signs of cancer spread to the brain. Visit the MRI page to read more.
• Positron emission tomography (PET) scans, often combined with CT scans, use images and radiotracer to look for cancer that has spread beyond the breast to other parts of the body. A specific type of PET scan called fluoroestradiol (FES) PET (brand name: Cerianna) works to confirm the presence of estrogen receptors on breast cancer cells in the body. Learn more on the PET scan page.

Biopsy to confirm MBC

Physical exams, imaging tests, and blood tests can provide information about whether MBC might be present in the body. But the most important MBC test is a confirming biopsy—a procedure that removes a piece of tumor tissue for examination in the lab. Biopsy is the only way to confirm that cancer has spread beyond the breast to another part of the body.

In MBC, biopsy can often be performed in common areas of breast cancer metastasis, including the liver, lungs, and sometimes the bones. In some cases, a biopsy is done at the same time as a CT scan to place the needle in the area of the tumor (typically done by an interventional radiologist). A biopsy might also be performed using surgery or a more minor procedure such as a needle biopsy without a scan, depending on the area of suspected metastasis.

Many doctors now perform a confirming biopsy followed by tests for hormone and HER2 receptors to find out if the cancer is hormone receptor-positive or HER2-positive or HER2-low. If MBC is a recurrence of an earlier breast cancer, biopsy is important for confirming whether hormone and HER2 status may have changed from the original diagnosis. This information can help you and your doctors decide on the most effective treatments for the cancer.

Hormone receptors and HER2 receptors are two of many breast cancer biomarkers (biological markers) that help doctors learn more about the cancer and inform treatment choices. You can learn more in the MBC biomarker tests section below.

If MBC is too difficult to biopsy

If other testing indicates that MBC may be present, but your healthcare team has not recommended a biopsy for you, it’s OK to request one or to ask your doctors why. In some cases, the site of metastasis may make biopsy very challenging. This can be true of metastases to the brain and the bone. In these cases, your doctors will rely on symptoms, scans, and blood work to confirm your diagnosis.

MBC biomarker tests

MBC tumor tissue and tumor DNA in the blood can be tested for biomarkers that help match the cancer to effective treatments. Biomarkers can also help determine eligibility for clinical trials. Biomarkers commonly identified in MBC include proteins and genetic mutations.

Here are some of tumor biomarker tests now being used in MBC:

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) tests use a special staining technique to confirm the presence of:

• Hormone receptors, which can confirm eligibility for endocrine therapy and certain targeted therapies
• HER2 receptors, which can confirm eligibility for HER2-targeted therapies
• A measure of mutations called MSI-High (microsatellite instability-high), which may determine eligibility for immunotherapy such as pembrolizumab (Keytruda) or dostarlimab (Jemperli)
• PD-L1 protein expression, which can determine eligibility for pembrolizumab

Fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) tests use a fluorescent dye and can be performed in combination with IHC testing to confirm the presence of HER2 receptors. FISH tests can also confirm NTRK gene fusion, a mutation that may indicate eligibility for treatment with larotrectinib (Vitrakvi) or entrectinib (Rozlytrek).

Next-generation sequencing (NGS)

Next-generation sequencing (NGS) tests, sometimes called broad molecular profiling tests, analyze tumor tissue for hundreds of genes. These tests look for genetic mutations and other biomarkers that can help match MBC to a specific treatment. Biomarkers NGS tests can find include:

• AKT1 mutations and/or PTEN alterations, which may mean eligibility for treatment with capivasertib (Truqap)
• ESR1 mutations, which can help determine eligibility for treatment with elacestrant (Orserdu)
• NTRK gene fusion, a mutation that may indicate MBC can be treated with larotrectinib or entrectinib
• PIK3CA mutations, which can determine eligibility for treatment with alpelisib (Piqray) or capivasertib (which can also be effective in the presence of other mutations, including in AKT, mTOR or PTEN genes)
• RET fusion, a DNA process that triggers MBC to grow and may help determine eligibility for a treatment called selpercatinib (Retevmo)
• TMB-High or microsatellite instability (MSI)-High, which can be associated with higher abnormal tumor proteins and may indicate eligibility for pembrolizumab

NGS tests can also be performed as blood tests (ctDNA tests), sometimes called liquid biopsy. These tests look for fragments of genetic information shed by cancer cells into the bloodstream.

The tumor cell genetic mutations mentioned above are not mutations that are inherited from a parent. Instead, these mutations happen over time, through environmental factors and as cancer cells change to try to resist treatments. These are sometimes called “somatic mutations.” The good news is that treatment advances can target somatic mutations.

PCR (polymerase chain reaction)

PCR (polymerase chain reaction) tests, which use a sample of blood, cancer tissue, or saliva to look for specific gene changes, can test for MSI-H and NTRK gene fusion.

Learn more about these biomarkers on the Biomarker testing page.

Tests to confirm an inherited breast cancer gene mutation

Knowing whether you have an inherited breast cancer mutation—a mutation that is passed down from a parent—is also important for understanding more about an MBC diagnosis. These are also called germline mutations.

Being born with an inherited gene mutation such as BRCA1 or BRCA2 that increases the risk of developing breast cancer is different than being diagnosed with breast cancer that develops non-inherited genetic mutations in the cancer cells over time.

Knowing whether you were born with an inherited breast cancer mutation can help you and your healthcare team understand more about an MBC diagnosis and treatment options:

• Breast cancer in people with inherited BRCA1-2 mutations can be more aggressive than other breast cancers.
• Having an inherited BRCA mutation may mean the cancer can be treated with PARP inhibitors, a type of targeted therapy.
• If you have an inherited BRCA1 mutation, the cancer is more likely to be triple-negative, which means it may be eligible for treatments including PARP inhibitors, sacituzumab govitecan (Trodelvy), and platinum-based chemotherapies.

If you have never had a blood test to look for inherited breast cancer mutations, ask your doctor to refer you to a genetic counselor. Learn more in our Genetics and family risk section.

Tests to monitor MBC treatment response

Some of the tests that indicate MBC may be present can also be used to look at whether cancer is growing or shrinking in response to treatment. These include:

Imaging tests

• Bone scans
• Chest x-rays
• CT scans
• PET scans
• MRI

Blood tests

• Blood chemistry tests
• Cancer antigen tests
• CBC tests
• Circulating tumor cell (CTC) tests
• ctDNA tests

Learn more about these tests in the Testing section.

Paying for MBC tests

Many tests for MBC are covered by health insurance, but some may not be, including some biomarker tests that are still being studied. If you have challenges finding coverage for a test, talk with your doctor about options. Your doctor may be able to help get insurance approval for a test.

You can also ask your doctor about the possibility of participating in a clinical trial that uses a test that could be beneficial. Participating in a trial might help reduce or even eliminate the cost of a test and/or treatment. Visit the Metastatic Trial Search page and talk with your doctor to learn about active trials.

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