Breast Cancer Biomarkers: What Your Results Mean

A biomarker is something that can be measured in your tumor, your blood or your genes that tells your care team something useful about your cancer. In breast cancer, biomarkers help answer three practical questions:

• Which treatments are likely to work, and which are not
• Whether you can safely skip a treatment, such as chemotherapy
• Whether the cancer has changed since your last test

Some biomarkers come from the tissue taken at your biopsy or surgery. Some come from a blood draw. Some come from a blood or saliva sample that checks the genes you inherited. Your report should say which kind of test it was, and that matters more than most people expect.

Biomarkers are features of your cancer, or of the genes you were born with, that tell your care team which treatments are likely to work. Every breast cancer should be tested for three of them: the estrogen receptor (ER), the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Those three results set your basic treatment plan. If the cancer has spread, more tests look for changes such as ESR1 and PIK3CA mutations, and each one can open the door to a specific targeted drug.

I'm holding my report right now. Where do I start?

Biomarker results usually show up on one of three kinds of report. Find the one you have.

Your pathology report

This is the report from your biopsy or surgery. It lists ER, PR and HER2, and often Ki-67. Every person with breast cancer should get these test results. If you have just had a biopsy, our post on what happens after a breast biopsy explains how the tissue gets to the lab and when results may come back.

A genomic test report

Names you might see are Oncotype DX, MammaPrint, Prosigna, EndoPredict and Breast Cancer Index. These will give you a score or a risk group. They are mostly used for early-stage cancer that is ER-positive and HER2-negative. These tests look at genes in the breast cancer tissue that may be changed, altered, activated or turned on. These results are specific for the breast cancer tissue, and are often different from the genes in the rest of your body, which are sometimes called “germ line” mutations.

A gene sequencing report

This report lists genes by name, such as BRCA1, BRCA2, PIK3CA, ESR1, AKT1 or PTEN. Look at the top of the report for two things. First, was it a tumor test or a germline test? A tumor test looks at changes in the cancer. A germline test looks at genes you were born with and could share with family. Second, was it a tissue test or a blood test? A blood test for cancer DNA is often called a liquid biopsy or a circulating tumor DNA (ctDNA) test.

Two terms on these reports can be confusing to many people:

• Variant allele frequency (VAF): The percentage printed next to a mutation on a blood test. It is the share of DNA pieces at that spot that carry the mutation. It is not a measure of how much cancer you have, and it is not a grade.
• Variant of uncertain significance (VUS): A finding on an inherited gene test that means a change was found, but no one knows yet whether it matters. A VUS is usually not used to make treatment decisions.

Which biomarkers should every breast cancer patient get tested for?

Estrogen receptor (ER)

This result tells you if estrogen signals the cancer to grow. Estrogen is a hormone your body makes.

Think of a receptor as a “lock” on the outside of a cancer cell. Estrogen is the key. When the key fits the lock, it tells the cell to grow.

• ER-positive: The cancer cells are confirmed to have these locks. About 3 out of 4 breast cancers are ER-positive. That matters, because medicines can block estrogen or lower how much of it your body makes. This is called hormone therapy. Tamoxifen and letrozole are two examples.
• ER-negative: The cancer cells do not have these locks. Hormone therapy will not help, so your team will plan other treatments.

Your report usually also shows a percentage. That is how many of the cancer cells have the ER-positive lock. If the number is between 1% and 10%, it is called ER-low. ER-low cancer often acts more like ER-negative cancer, so it’s important to ask your doctor how they plan to treat it.

Progesterone receptor (PR)

This result tells you if progesterone, another hormone in the body, helps the cancer grow.

PR works the same way as ER. It is a second lock, for a second key. Your doctor looks at ER and PR together. Together, they are called your hormone receptor status, or HR status. If either one is positive, the cancer is called HR-positive.

If your cancer is ER-positive but PR-negative, it may grow a little faster. Your care team will consider this when planning your treatment.

Human epidermal growth factor receptor 2 (HER2)

This result tells you if the cancer has too much of a protein called HER2.

All breast cells have some HER2. It works like a gas pedal for growth. Some cancers have far too much of it, so the pedal gets pushed down hard and the cells grow fast. There are medicines made to target HER2 directly.

Your report gives HER2 a score from 0 to 3+. Here is what each score means:

• 3+: HER2-positive. Medicines that target HER2, like trastuzumab (Herceptin) and pertuzumab (Perjeta), will potentially be part of your treatment. Learn more about TCHP, a common treatment for HER2-positive cancer.
• 2+: Not clear yet. The lab runs a second test, called ISH or FISH. If that test is positive, the cancer is HER2-positive. If not, it is HER2-low.
• 1+: HER2-low.
• 0, with a small amount of HER2 in a few cells: HER2-ultralow.
• 0, with no HER2 seen: HER2-zero.

HER2-low and HER2-ultralow used to be called HER2-negative. Now they matter if the cancer spreads. They can make you a candidate to get a medicine called trastuzumab deruxtecan (Enhertu). If a report just says "HER2-negative," ask your doctor for the exact score.

What ER, PR and HER2 add up to

Your three results put your cancer into one of three main groups. Each group is treated in a different way.

• HR-positive, HER2-negative: The most common group. Treatment usually includes hormone therapy.
• HER2-positive: Treatment usually includes medicines that target HER2. These cancers can be HR-positive too.
• Triple-negative: ER, PR and HER2 are all negative. Hormone therapy will not help, so treatment usually includes chemotherapy, and sometimes immunotherapy.

Ki-67

Ki-67 estimates how many cancer cells are dividing at the time of the test. A higher number means faster growth. It helps tell slower-growing HR-positive cancers apart from faster-growing ones. For some people with higher-risk early-stage cancer, it helps decide whether to add drugs such as abemaciclib (Verzenio) or ribociclib (Kisqali) after surgery. Labs measure Ki-67 in different ways, so a single Ki-67 number is less reliable than your ER, PR or HER2 result.

Can a genomic test tell me whether I need chemotherapy?

Often, yes, if your cancer is early-stage, HR-positive and HER2-negative. A genomic test looks at a group of genes in the tumor and estimates the chance the cancer comes back. The most widely used is Oncotype DX, which gives a Recurrence Score from 0 to 100. Others include MammaPrint, Prosigna and EndoPredict. A related test, Breast Cancer Index, is mostly used later on, to help decide whether to stay on hormone therapy past five years.

The main job of these tests is to answer one question: will chemotherapy add enough benefit to be worth its side effects? Two large trials, TAILORx and RxPONDER, showed that many people with lower scores can safely skip chemotherapy and take hormone therapy alone. What counts as a lower score depends on your age, whether you have gone through menopause, and whether cancer was found in your lymph nodes. So ask your oncologist what your score means for you, rather than comparing it with someone else's.

Should I get genetic testing for inherited genes like BRCA?

Germline genetic testing checks the genes you were born with, using a blood or saliva sample. It is a separate test from the one done on your tumor. Everyone with breast cancer that has spread should be offered it, and many people with early-stage breast cancer are offered it too. If no one has brought it up, it is a fair question to ask.

BRCA1 and BRCA2

Inherited BRCA mutations raise the risk of breast and ovarian cancer, and they change treatment. In early-stage, HER2-negative breast cancer with a high chance of coming back, a year of a pill called olaparib (Lynparza) after standard treatment lowers that chance. If the cancer has spread, a BRCA mutation can make you eligible for a type of drug called a PARP inhibitor, either olaparib or talazoparib (Talzenna). A BRCA result can also shape surgery choices, and it matters for your blood relatives, including both female and male relatives.

Other inherited genes

Gene panels also check genes such as PALB2, CHEK2, ATM, TP53, PTEN and CDH1. These mostly affect screening and cancer risk for you and your family. PALB2 is starting to factor into PARP inhibitor decisions as well. A genetic counselor can explain what your result means for you and for your relatives.

If my breast cancer has spread, what other biomarker tests should I expect?

This is where biomarker testing has changed the most in the last few years, especially for HR-positive, HER2-negative cancer, the most common type.

The usual first treatment for HR-positive, HER2-negative metastatic breast cancer is hormone therapy plus a drug called a CDK4/6 inhibitor: ribociclib (Kisqali), palbociclib (Ibrance) or abemaciclib (Verzenio). Over time, cancer can find ways around treatment. Biomarker tests track those changes, and several now point to a specific next drug. Your care team will also usually want a biopsy of a spot where the cancer has spread, when that can be done safely, to recheck ER, PR and HER2, since they can be different from the original tumor.

PIK3CA, AKT1 and PTEN

These three genes control a growth signal inside the cell. Think of PIK3CA and AKT1 as parts of the accelerator and PTEN as the brake. A mutation in PIK3CA or AKT1 jams the accelerator down. Losing PTEN takes the brake off. Either way, the cell gets a constant signal to grow.

About 4 in 10 HR-positive, HER2-negative breast cancers have a PIK3CA mutation. These changes are usually there from the start, so a test on the tissue from your original diagnosis may already show one. If a blood test finds nothing, your team may test tissue too.

Drugs that block this signal are always given with hormone therapy, because blocking the signal helps hormone therapy work again:

• Alpelisib (Piqray): For a PIK3CA mutation, given with fulvestrant
• Inavolisib (Itovebi): For a PIK3CA mutation, given with palbociclib and fulvestrant, when the cancer came back during, or soon after, hormone therapy following surgery
• Capivasertib (Truqap): For a change in PIK3CA, AKT1 or PTEN, given in tandem with fulvestrant
• Gedatolisib (Revtorpyk): Approved in July 2026 for cancer with no PIK3CA mutation, after treatment with a CDK4/6 inhibitor and an aromatase inhibitor. It is given by IV with fulvestrant, with or without palbociclib.

Side effects vary by drug. High blood sugar is a commonly reported side effect with alpelisib, inavolisib and capivasertib, because this same signal helps your body handle insulin. You will usually have fasting blood sugar and HbA1c checks before starting treatment and regular checks during treatment. If you have diabetes or prediabetes, make sure your oncologist knows. Rash and diarrhea are also common. With gedatolisib, mouth sores are the most common side effect and high blood sugar is less frequent.

ESR1

ESR1 is the gene that makes the estrogen receptor. ESR1 mutations are rare when breast cancer is first found. They usually show up later, during treatment with an aromatase inhibitor such as letrozole, anastrozole or exemestane.

Aromatase inhibitors work by starving the cancer of estrogen. Under that pressure, the cancer can develop an ESR1 mutation that locks the receptor in the "on" position, so it keeps driving growth with no estrogen at all. At that point the aromatase inhibitor stops working well, but the cancer still depends on the receptor. So the next move is to go after the receptor itself. Drugs called SERDs (selective estrogen receptor degraders) and newer receptor degraders attach to the receptor and get it broken down.

Because ESR1 mutations develop during treatment, a negative result at diagnosis does not tell you much later on. National treatment recommendations call for testing for ESR1 each time the cancer grows on hormone therapy, preferably with a blood test. Approved options for ESR1-mutated cancer include:

• Elacestrant (Orserdu): A pill, after at least one earlier hormone therapy
• Imlunestrant (Inluriyo): A pill, after at least one earlier hormone therapy, taken alone or, since September 2026, with abemaciclib
• Vepdegestrant (Veppanu): A pill approved in May 2026, after at least one earlier hormone therapy. It is a newer kind of drug that tags the receptor for the cell's own disposal system.
• Camizestrant (Etcamah): A pill approved in September 2026, given with a CDK4/6 inhibitor. It is for people whose blood test picks up a new ESR1 mutation while they are still on their first aromatase inhibitor and CDK4/6 inhibitor, before scans show the cancer growing.

Camizestrant is the first approval built around routine blood tests during treatment. It received accelerated FDA approval, and experts still disagree about how often to run these blood tests and whether switching early is better than switching when scans change. That is a reasonable thing to talk through with your oncologist.

Fulvestrant (Faslodex), an older SERD given as a shot, works whether or not there is an ESR1 mutation.

Another pill, giredestrant, is under FDA review and is not yet approved as of the time of writing. One application is for use with everolimus (Afinitor) in ESR1-mutated cancer that has grown after hormone therapy and a CDK4/6 inhibitor. A second is for early-stage ER-positive, HER2-negative breast cancer after surgery, where an ESR1 mutation would not be required. FDA decisions on both are expected by the end of 2026, so ask your oncologist whether either has been approved by the time you read this.

HER2-low and HER2-ultralow

If your cancer is HER2-low or HER2-ultralow and has grown after at least one hormone-based treatment, trastuzumab deruxtecan (Enhertu) may be an option. Two related drugs, datopotamab deruxtecan (Datroway) and sacituzumab govitecan (Trodelvy), are also used later in treatment. These do not need a separate biomarker test.

Which treatments each result can open up

Result	What it may open up	Type of test
PIK3CA mutation	Alpelisib, inavolisib or capivasertib, each with hormone therapy	Tissue or blood
AKT1 or PTEN change	Capivasertib with fulvestrant	Tissue or blood
No PIK3CA mutation	Gedatolisib with fulvestrant, with or without palbociclib	Tissue or blood
ESR1 mutation	Elacestrant, imlunestrant, vepdegestrant or camizestrant	Blood preferred, repeated over time
Inherited BRCA1 or BRCA2 mutation	Olaparib or talazoparib	Germline blood or saliva
HER2-low or HER2-ultralow	Trastuzumab deruxtecan	Tissue

Which biomarkers matter for triple-negative breast cancer?

Triple-negative breast cancer has no ER, PR or HER2 to target, so a different set of biomarkers comes into play.

PD-L1

PD-L1 is a protein on cancer cells and nearby immune cells. If triple-negative cancer has spread and the PD-L1 score (called CPS) is 10 or higher, the immunotherapy pembrolizumab (Keytruda) can be added to chemotherapy. For early-stage triple-negative cancer, pembrolizumab is given before and after surgery whatever the PD-L1 result, so the test is not needed to qualify.

BRCA1 and BRCA2

Inherited BRCA mutations are more common in triple-negative breast cancer. A positive result can make PARP inhibitors an option, as described above.

TROP2

TROP2 is the protein that sacituzumab govitecan (Trodelvy) and datopotamab deruxtecan (Datroway) attach to. Nearly all triple-negative cancers have it, so you do not need a TROP2 test to get these drugs.

Rare findings on large gene panels

Large panels sometimes find changes called NTRK fusions, MSI-high or mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-high). These are rare in breast cancer, but each can make certain drugs an option no matter where the cancer started. For more on where treatment is heading, listen to Dr. Sara Tolaney on the next era of metastatic triple-negative breast cancer.

What can a biomarker test not tell you?

It cannot tell you your outlook on its own

A biomarker shows which treatments are likely to work. Your outlook depends on many other things, including stage, how the cancer responds to treatment, and your overall health.

A negative blood test is not always the final word

Some cancers shed very little DNA into the blood. A blood test can miss a mutation that is really there. If a blood test comes back negative or unclear, your team may test cancer tissue.

A tumor test does not tell you what you inherited

If a tumor test finds a BRCA mutation, you need a separate germline test to know whether you were born with it. That answer matters for your family.

An old result may not describe the cancer today

Cancer can change over time. ESR1 mutations appear during treatment, and ER, PR and HER2 can differ between the original tumor and a spot where the cancer has spread. Results from two years ago may not reflect what is happening now.

Tumor marker blood tests are for tracking, not diagnosis

CA 15-3, CA 27.29 and CEA are blood tests sometimes used to follow metastatic breast cancer over time. They are not used to diagnose breast cancer, and a single rise is not proof the cancer is growing.

Not every finding has a matching drug yet

Some results do not have an approved treatment. They may still make you a candidate for a clinical trial. Read more about what clinical trials are and how to find one.

What should I ask my care team about my biomarkers?

Bring these to your next appointment. You do not need to ask every one.

Medical oncologist

• What are my ER, PR and HER2 results, and what group does that put my cancer in?
• Was my HER2 score 0, 1+, 2+ or 3+? Does HER2-low or HER2-ultralow apply to me?
• Is a genomic test like Oncotype DX right for me, and how will the result change my plan?
• Has my tumor been tested for PIK3CA, AKT1, PTEN and ESR1? If not, when will it be?
• Was my test done on tissue or on blood? If blood came back negative, should we test tissue?
• How often will I be retested, and what result would make you change my treatment?
• Do any of my results make me a fit for a clinical trial?
• If I start a drug that can raise blood sugar, how will we watch for that?

Breast surgeon

• Do my biomarker results mean I should have treatment before surgery?
• Will my genetic test result change my surgery options?
• Will the tissue from my surgery be retested for ER, PR and HER2?
• Will my surgery tissue be sent for a genomic test, and who orders it?
• Is enough tissue being saved in case I need more tests later?

Genetic counselor

• What did my germline test find, and what does each result mean for me?
• Is anything on my report a variant of uncertain significance? What happens if it gets reclassified?
• Which of my relatives should consider testing, and how do I tell them?
• Does my result change my cancer screening going forward?
• Does my result make any treatment an option for me?

Also Read:

• I just got a cancer diagnosis. What happens next?
• What happens after a breast biopsy?
• What is TCHP chemotherapy?
• Taking a break from tamoxifen: when, why and what to expect
• How antibody-drug conjugates are changing cancer care, with Dr. Milana Dolezal

Frequently asked questions

Q: What are the main biomarkers for breast cancer?

Ans - The main breast cancer biomarkers are the estrogen receptor (ER), progesterone receptor (PR) and HER2, which are tested on every breast cancer. Other common ones are Ki-67, genomic tests such as Oncotype DX, inherited genes such as BRCA1 and BRCA2, and, when cancer has spread, tumor mutations such as PIK3CA, AKT1, PTEN and ESR1. For triple-negative cancer, PD-L1 also matters.

Q: What does it mean that my breast cancer is HER2-low?

Ans - HER2-low means your cancer scored 1+, or 2+ with a negative ISH test. It is still treated as HER2-negative at first. If the cancer spreads, HER2-low on the tumor tissue suggests that you may benefit from treatment with trastuzumab deruxtecan (Enhertu), a drug that did not used to be an option for HER2-negative cancer.

Q: What does it mean that my tumor has an ESR1 mutation?

Ans - An ESR1 mutation means the estrogen receptor in your cancer is stuck in the "on" position, usually after treatment with an aromatase inhibitor. Aromatase inhibitors tend to stop working well at that point. Drugs that break down the receptor, such as elacestrant, imlunestrant, vepdegestrant and camizestrant, are made for this situation.

Q: Is a PIK3CA mutation inherited?

Ans - No. PIK3CA mutations found in breast cancer are almost always in the tumor only, not in the genes you were born with, so they are not passed to your children. They matter because they can make drugs such as alpelisib, inavolisib or capivasertib an option.

Q: How accurate is a liquid biopsy for breast cancer?

Ans - A liquid biopsy is good at finding mutations when the cancer releases enough DNA into the blood, and it is the preferred way to test for ESR1. It can miss a mutation when the cancer sheds very little DNA. A negative result may need a follow-up tissue test.

Q: Will I need to be retested?

Ans - If your cancer has spread, probably yes. ESR1 mutations develop during treatment, so testing is usually repeated each time the cancer grows on hormone therapy. Your team may also biopsy a new spot to recheck ER, PR and HER2.

Q: How long do biomarker results take?

Ans - ER, PR and HER2 results usually come back with your pathology report, within about a week of a biopsy. Genomic tests such as Oncotype DX and blood-based mutation tests usually take one to three weeks. Ask your care team when to expect each result and how you will hear about it.