Breast Cancer Biomarkers and Biomarker Tests
Biomarkers, also called tumor markers, are molecules that are a sign of a process or disease. They’re found in blood or other body fluids, tissue, and cells. Biomarkers can be proteins, hormones, genes, genetic mutations, or other molecules.
If you’ve been diagnosed with breast cancer, biomarkers may be used in a number of ways:
Biomarkers help doctors figure out the subtype of the cancer. Knowing the breast cancer subtype helps you and your doctor decide on the best treatments for your unique situation.
Biomarkers help doctors figure out how likely early-stage breast cancer is to come back (recur) and make decisions about whether treatments after surgery would offer benefits.
Biomarkers can help doctors judge how likely the cancer is to respond to a certain treatment.
Biomarkers may help doctors monitor how the cancer is responding to treatment.
Biomarkers may help determine your prognosis.
Biomarkers are used in research to help understand the biology of cancer and develop new treatments.
If you’ve been diagnosed with metastatic breast cancer — cancer that has spread to parts of the body away from the breast, such as the bones or liver — testing for certain biomarkers can help identify standard treatment options as well as experimental treatments and clinical trials that may be appropriate for your situation.
Breast cancer biomarker tests
Breast cancer biomarker tests are done on a sample of the cancer tumor or on a sample of your blood or tissue.
There are a number of different tests used to look for breast cancer biomarkers — no one test can find all biomarkers. Doctors may choose to test for biomarkers that are important for your diagnosis or treatment.
Because there are many different biomarkers, there are many types of biomarker tests, which can be confusing. Besides being called tumor marker tests, biomarker tests also may be called:
tumor tests
tumor genetic tests
genomic profiling
molecular tests
molecular profiling
somatic tests
somatic mutation tests
tumor subtype tests
Testing for breast cancer biomarkers is different from genetic testing. Genetic testing is done on a sample of non-cancerous tissue, such as your blood, saliva, or other tissue, to figure out if you have an inherited genetic mutation from your mother or your father linked to a higher risk of breast or other cancers.
Certain breast cancer biomarker tests look for genetic mutations in the cancer tumor that aren’t inherited. These mutations happen over the course of your life. They’re the result of the natural aging process or exposure to things in the environment, like cigarette smoke. These acquired mutations are called somatic mutations. Testing for somatic mutations in a cancer tumor may be called somatic testing or tumor genetic testing.
In breast cancer, testing for three biomarkers is routinely done on every tumor: estrogen receptor status, progesterone receptor status, and HER2 status. The results of these tests will be in your pathology report.
There are two hormone receptors that every breast cancer will be tested for.
Estrogen receptor status: If the breast cancer has receptors for the hormone estrogen, it’s called estrogen receptor-positive. This means the cancer is likely to respond to hormonal therapy medicines such as tamoxifen or an aromatase inhibitor.
Progesterone receptor status: If the breast cancer has receptors for the hormone progesterone, it’s called progesterone receptor-positive and is also likely to respond to hormonal therapy medicines.
If a breast cancer tests positive for estrogen receptors, progesterone receptors, or both, it’s called hormone receptor-positive. If the cancer tests negative for both estrogen and progesterone receptors, it’s called hormone receptor-negative.
Your doctor also will have the breast cancer’s HER2 status tested. The HER2 gene makes HER2 proteins, which are receptors on breast cells that make the cancer grow. Some breast cancers have too many copies of the HER2 gene, which make too much HER2 protein. This makes breast cells grow and divide uncontrollably. These cancers are called HER2-positive and are likely to respond to anti-HER2 therapies.
Cancers with normal levels of HER2 proteins are considered HER2-negative. Still, more than half of breast cancers considered HER2-negative have some extra HER2 proteins, just not enough to be considered HER2-positive. These are called HER2-low or HER2-ultralow.
Doctors may test a breast cancer tumor for other biomarkers, but these tests are not done on every breast cancer. Doctors decide to do these tests based on the cancer’s other characteristics — for example, if the cancer is early-stage or metastatic, or if it’s triple-negative or hormone receptor-positive and has grown during treatment.
PD-L1 status: If you’ve been diagnosed with advanced-stage or metastatic triple-negative breast cancer, your doctor may do a test to see if the cancer is PD-L1-positive to figure out if the immunotherapy medicine Keytruda (chemical name: pembrolizumab) would be beneficial.
Genomic testing, also called genomic profiling, may be done on certain early-stage breast cancers to figure out if the cancer has a high or low recurrence risk. If the risk of recurrence is high, more treatments — such as chemotherapy or or five more years of hormonal therapy for a total of 10 years of hormonal therapy treatment — may be recommended.
ESR1 mutation status: The ESR1 gene tells your body to make estrogen receptors. These receptors tell estrogen receptor-positive breast cancers to grow in the presence of estrogen. In many cases, metastatic, estrogen receptor-positive breast cancer develops a mutation in the ESR1 gene during treatment with hormonal therapy. This mutation makes the cancer resistant to hormonal therapy – so the medicine Orserdu (chemical name: elacestrant) may be recommended.
PIK3CA mutation status: The PIK3CA gene tells your body to make the PI3K protein, which helps make sure cells get the energy they need to grow. When the PIK3CA gene is mutated, the instructions the gene gives your body are wrong and the PI3K protein doesn’t work the way it should, which can allow cancer cells to survive and grow. If metastatic, hormone receptor-positive, HER2-negative breast cancer grows after being treated with hormonal therapy and has a PIK3CA mutation, the medicines Piqray (chemical name: alpelisib) or Truqap (chemical name capivasertib) may be recommended.
AKT1 and PTEN mutation status: The AKT1 and PTEN genes make proteins that help control how quickly cells grow and divide. When one or both of these genes is mutated, cells can grow and divide uncontrollably. If metastatic, hormone receptor-positive, HER2-negative breast cancer grows after being treated with hormonal therapy and has either of these mutations, Truqap may be recommended.
BRCA1 and BRCA2 mutation status: If certain HER2-negative breast cancers have a mutation in the BRCA1 or BRCA2 gene, the medicines Lynparza (chemical name: olaparib) or Talzenna (chemical name: talazoparib) may be recommended.
Tumor mutational burden: The mutational burden in a breast cancer tumor is the number of genetic mutations found in the cancer cells’ DNA. If metastatic breast cancer has a high tumor mutational burden and has grown after previous treatment, Keytruda may be recommended.
Ki-67 levels: Ki-67 is a protein that helps control how quickly cells divide, called the rate of cell growth by doctors. Breast cancer cells with higher Ki-67 levels tend to divide and grow more quickly. If a cancer is growing quickly, it is likely to be more aggressive, and treatments such as chemotherapy may be recommended.
Deficient DNR mismatch repair mutation (dMMR): dMMR breast cancers have mutations in some of the genes that affect how DNA is repaired. If the cancer is advanced-stage and has grown during or after previous treatments, the immunotherapy medicines Keytruda or Jemperli (chemical name: dostarlimab-gxly) may be recommended. Fewer than 1% of breast cancers have the dMMR biomarker.
Microsatellite instability-high (MSI-H): Like dMMR tumors, MSI-H breast cancer cells have mutations that affect how DNA is repaired. If the cancer is metastatic and has grown during earlier treatment, Keytruda may be recommended.
CA 15-3 levels: Cancer antigen 15-3 (CA 15-3) is a protein that cells produce in response to changes in the body. Higher levels of CA 15-3 may mean certain cancers, including breast cancer, are present.
CA 27-29 levels: Cancer antigen 27-29 (CA 27-29) is a protein that can be released by breast cancer. Higher levels of CA 27-29 can mean that metastatic breast cancer is growing.
CA 125 levels: Cancer antigen 125 (CA 125) is a protein that’s mainly associated with ovarian cancer, but higher levels may mean breast cancer has recurred (come back).
CEA levels: Carcinoembryonic antigen (CEA) is a protein that can indicate colon cancer. It can be used to determine if breast cancer has spread to other parts of the body.
Broad molecular profiling: Also called somatic testing, molecular profiling, next-generation sequencing, and comprehensive genomic profiling, these tests look at a large number of genes in a cancer tumor to see if there are somatic mutations. Right now, broad molecular profiling tests are mainly done on metastatic breast cancer tumors to see if there are approved or experimental targeted therapy medicines that may be effective. FoundationOne CDx and Guardant360 CDx are two examples of broad molecular profiling tests that have been approved by the Food and Drug Administration (FDA).
Circulating tumor DNA (ctDNA): Circulating tumor DNA are fragments of the cancer cells’ DNA that enter the bloodstream. A blood test, also called a liquid biopsy, is done to look for ctDNA. Finding ctDNA in the bloodstream also can let doctors know that cancer cells are starting to divide and grow. Because ctDNA may be in the blood even if just a few cancer cells are present, the test can allow doctors to diagnose cancer recurrence before you have any physical symptoms, such as a lump or pain. Signatera is one ctDNA test that may be done on stage II or higher breast cancer after surgery. Right now, the best way to manage a positive ctDNA test in someone who doesn’t have recurrent or metastatic breast cancer isn’t clear, but it’s being studied in clinical trials. Broad molecular profiling tests also may be used to check for ctDNA.
Scientists are always looking for more biomarkers that can help you and your doctor decide on the best treatments or decide how well a treatment is working. The biomarkers below are being studied in clinical trials, so you may hear about them.
Circulating tumor cells (CTC): Circulating tumor cells are cancer cells that have broken off from the tumor and are in the bloodstream. Like ctDNA, testing for CTCs is also done with a blood test or liquid biopsy. Doctors are still figuring out the best way to use circulating tumor cell information to make treatment decisions for metastatic breast cancer.
CellSearch is a circulating tumor cell test approved by the FDA for metastatic breast cancer. According to the company, doctors can use the results to monitor how the metastatic breast cancer responds to treatment, but research is ongoing.
Tumor-infiltrating lymphocytes (TIL) and stromal tumor infiltrating lymphocytes (sTIL): Tumor infiltrating lymphocytes (TILs) are white blood cells, a type of immune cell, that have moved from the bloodstream into a cancer tumor. Stromal tumor-infiltrating lymphocytes are the same immune cells but are found in the stroma, the connective tissue surrounding cancer cells. To detect and measure TILs and sTILs, scientists use a special stain on a piece of cancer tumor that makes the TILs and sTILs visible.
TILs and sTILs have the ability to kill cancer cells. Some research suggests that the more TILs or sTILs in a cancer tumor, the better the outcome. Other clinical trials are looking at collecting TILs from cancer tumors, growing more of them in a lab, and then infusing them back into the person to treat the cancer. Still, it’s important to know that not all breast cancer tumors have high levels of TILs or sTILs, and doctors are trying to understand why this is.
The cost of breast cancer biomarker testing varies widely and depends on the type of test you get and your insurance plan.
Biomarker tests routinely done on every breast cancer are usually covered by insurance.
Biomarker tests that may be done, depending on cancer characteristics, are often, but not always covered by insurance.
Biomarker tests still under investigation are usually not covered by insurance.
For people diagnosed with metastatic breast cancer, some biomarker tests are covered by Medicare and Medicaid.
Many clinical trials involve biomarker testing. If you join a clinical trial, the cost of biomarker testing might be included.
Listen to the episode of The Breastcancer.org Podcast featuring Triage Cancer CEO Joanna Doran discussing laws to ensure more comprehensive insurance coverage for biomarker testing.
This content is supported in part by Lilly, AstraZeneca, Biotheranostics, Inc. A Hologic Company, Pfizer, Gilead, Exact Sciences, Novartis, Seagen, and MacroGenics.
— Last updated on June 10, 2025 at 4:10 PM