Biomarkers, targeted and immunotherapies for breast cancer
This section covers the following topics:
- Tumor testing for treatment selection
- Genetic testing for inherited mutations for treatment selection
- Tumor testing for prognosis
- PARP inhibitors
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
tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. 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 Testing section for more information.
(ER and PR) and
After breast cancer tissue is removed by surgery or biopsy, all breast cancers should be tested for three common biomarkers:
- Hormone receptors (): These are also sometimes called and progesterone receptors (ER/PR).
- Cancers that test positive for and progesterone receptors are known as . They may also be called . These cancers are often treated with hormone therapies.
- Cancers that test negative for and progesterone receptors are known as or HR-negative. These cancers are not usually treated with hormone therapy.
- is a protein that is found on all breast cancer cells. Tests measure the amount of protein in the tumor and provide a score from 0 to 3+.
- Cancers with a score of 3+ are considered . 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 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 . These cancers are not treated with anti-HER2 agents.
Biomarkers for Advanced Breast Cancer
For people with advanced breast cancer, additional 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 for a specific is sometimes called a . Some tests look for only one at a time. Examples of single tests for breast cancer include:
- ESR1 mutation: Testing for ESR1 can help find people who will benefit from treatment with the SERD, Oserdu (olacestrant).
- PIK3CA: Testing for this gene in advanced ER-positive, breast cancer can help find people most likely to respond to the medication PIQRAY (alpelisib).
- PD-L1: Testing for the protein can help find people with advanced () who are most likely to respond to the drugs Tecentriq (atezolizumab) and Keytruda (pembrolizumab).
- HER2-low: Testing for is standard-of-care for all breast cancer. In the past, cancers were labeled or . New research shows that the drug Enhertu (trastuzumab-deruxtecan or T-DXd) can be used to treat advanced breast cancers that are HER2-low.
If you have advanced or breast cancer and were told your cancer is or triple-negative, it's important to find out more about your test scores. Cancers that were labeled as in the past may be HER2-low. Some people with advanced or HER2-low cancers may benefit from the drug Enhertu.
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 tumor tests for breast cancer include:
- Tempus xT
Genetic testing for an may be used to guide treatment selection for people diagnosed with breast cancer.
- People with advanced breast cancer who test positive for an inherited or mutation may benefit from treatments known as PARP inhibitors. Two PARP inhibitors—Lynparza and —are approved as for treating advanced breast cancer in people with a or mutation.
- Lynparza may be used to as after treatment for people with an inherited or mutation who have 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.
These tests are used for people with 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™
PARP inhibitors work by blocking a protein used by cells to repair damaged . They were initially developed to treat cancers in people with an inherited gene mutation or mutation.
- For breast cancer, two PARP inhibitors have received FDA-approval as for treating people with an inherited mutation:
- Lynparza ()
- For people with early breast cancer at high risk for recurrence:
- Lynparza may be used as after chemotherapy in people with an inherited or mutation. Although the has not yet approved Lynparza for this indication, doctors may still prescribe it off-label. Several expert guidelines now include recommendations for Lynparza for patients with high-risk, early breast cancer and a or mutation.
Research is ongoing to learn if PARP inhibitors are affective for treating breast cancer in other situations, including:
- people with an in a different gene that repairs damage (for example: , or ).
- people who do not have an inherited gene mutation, but their tumor tested positive for an acquired mutation in a gene that repairs damage.
Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. Immune checkpoint inhibitors are a type of used to treat several types of cancer, including breast cancer. Some cancer cells produce proteins which can switch off immune cells and keep them from attacking. Immune checkpoint inhibitors are drugs that prevent cancer cells from switching off immune cells. This allows the immune system to find, unmask and destroy cancer cells. Immune checkpoint inhibitors are approved for treatment of the following types of breast cancer.
- Keytruda (pembrolizumab) is approved in combination with chemotherapy for treatment of that is or locally recurrent and unresectable that tests positive for a called .
- Keytruda is approved for the treatment of triple-negative breast cancer that is at high risk for recurrence. In this setting, Keytruda is used along with chemotherapy as therapy before surgery. Following surgery, Keytruda is continued alone.
Targeted therapies are treatments that act on certain molecules or targets within cancer cells to prevent the cancer cells from growing or spreading while sparing normal cells. Tumor testing can help doctors identify the patients most likely to benefit from a . Common targeted therapies used in breast cancer include:
- breast cancers are often treated with drugs that target the protein. Common anti-HER2 therapies include Herceptin (trastuzumab), Perjeta (pertuzumab) and Tukysa (tucatinib), Phesgo (pertuzumab, trastuzumab and hyaluronidase) and Enhertu (fam-trastuzumab-deruxtecan-nxki or T-DXd).
- HER2-low advanced or breast cancers may be treated with the anti-HER2 drug Enhertu.
- People with advanced breast cancer are often treated with CDK4/6 inhibitors. CDK4/6 inhibitors target proteins found in some breast cancers called CDK inhibitors. The three CDK4/6 inhibitors approved for use in breast cancer are: Ibrance (palbociclib), Kisqali (ribociclib) and Verzenio (abemaciclib).
- The drug Piqray (alpelisib) is approved for people who have advanced, breast cancer who test positive for a tumor called PIK3CA. PIK3CA is an acquired gene mutation found in some ER-positive breast cancers.
Table of targeted and immunotherapies for breast cancer
|Name of drug||Cancer||Indication||Type of agent|
|Early||The treatment of breast cancer||overexpression ()||Antibody targeting receptors|
|Locally advanced, inflammatory or early||Combined with Herceptin (trastuzumab) and docetaxel as treatment before surgery ()||overexpression ()||Antibody targeting receptors|
|Phesgo (pertuzumab, trastuzumab combined injection)||Early||
Before surgery () for tumors larger than 2 cm or node-positive or after surgery ( treatment) for early breast cancer that has a high likelihood of coming back
|overexpression ()||Antibody targeting receptors|
|Keytruda (pembrolizumab)||Early TNBC at high risk for recurrence||Before surgery Keytruda is used along with chemotherapy as therapy. Following surgery, Keytruda is continued alone.||Triple-negative
|Immune checkpoint inhibitor|
|Lynparza ()||Early breast cancer at high risk for recurrence||Given for one year as after completion of or and local treatment (surgery and, or radiation).||or inherited mutation|
|Early||therapy for people with early breast cancer who still have disease after taxane and treatment with Herceptin||overexpression ()||Antibody targeting receptors|
Treatment for people who have received a prior anti-HER2 therapy for breast cancer or had their breast cancer come back during or within 6 months of completing treatment for their breast cancer
|overexpression ()||Antibody-drug conjugate (chemotherapy attached to antibody to )|
|Enhertu (fam-trastuzumab-deruxtecan-nxki)||Treatment for people with tumors that are HER2-low who received chemotherapy in the setting and whose cancer no longer responds to hormonal therapy||HER2-low||Antibody-drug conjugate (chemotherapy attached to antibody to )|
|For patients who previously received Herceptin and chemotherapy, separately or in combination. Patients should have either received therapy for disease, or developed disease recurrence during or within six months of completing therapy||overexpression ()||Antibody targeting receptors|
|Tukysa (tucatinib)||In combination with Herceptin (trastuzumab) to treat cancer which has progressed after at least one prior treatment with an anti-HER2 treatment in the setting||overexpression ()||Kinase inhibitor|
|Trodelvy (sacituzumab govitecan-hziy)||For breast cancer that progressed, recurred or did not respond to at least two previous lines of treatment||Triple-negative (, )||Antibody-drug conjugate (chemotherapy attached to antibody found in )|
|Combined with Aromasin (exemestane) for postmenopausal women with advanced breast cancer which progressed with Femara (letrozole) or Arimidex (anastrozole)|| and
|MTOR inhibitor (type of kinase inhibitor)|
Used alone to treat men or postmenopausal women with , breast cancer with an ESR1 mutation, which progressed after at least one line of hormone therapy therapy
|, , ESR1 mutation||SERD (selective receptor degrader or downregulator)|
|Combined with Faslodex (fulvestrant) as treatment in men or post-menopausal women who progressed on or after treatment with hormone therapy.||
and and PIK3CA-positive
|Verzenio (abemaciclib)||Used alone to treat men or women with breast cancer that has progressed after treatment with hormone therapy and chemotherapy in the setting.||
|Combined with Faslodex (fulvestrant) as treatment in women whose disease progressed following endocrine therapy.||and||CDK4/6 inhibitor|
|Combined with an aromatase inhibitor as treatment of
advanced cancer as initial hormone therapy in postmenopausal women or in men
|Combined with Faslodex (fulvestrant) as treatment in postmenopausal women or in men whose disease progressed following endocrine therapy||and||CDK4/6 inhibitor|
|Combined with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women as initial hormone based therapy||and||CDK4/6 inhibitor|
|Combined with Faslodex (fulvestrant) for the treatment of postmenopausal women, as initial hormone based therapy.||and||CDK4/6 inhibitor|
|Lynparza ()||For treatment of patients who have previously received chemotherapy, or hormone therapy for patients with hormone receptor ()-positive disease||or mutation and|
|For treatment of breast cancer||or mutation and|
|Keytruda (pembrolizumab)||Combined with chemotherapy for treatment of locally recurrent unresectable or triple negative breast cancer||Triple-negative ( and )
|Immune checkpoint inhibitor|
The following organizations offer peer support services for people with, or at high risk for breast cancer:
- FORCE peer support:
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Connect online with our Private Facebook Group.
- Join our virtual and in-person support meetings.
- Other organizations that offer breast cancer support:
The following are studies enrolling people with early breast cancer.
- NCT04584255: Treating BRCA, or PALB2-Associated Breast Cancer with a () and (Dostarlimab). This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with or mutations.
- NCT04915755: Screening for Cancer in the Blood after Treatment for TNBC and/or a Mutation; Followed by Study Comparing with for People with Cancer found in their Blood (ZEST). ZEST has two parts, a screening portion that will look for evidence of cancer cell in the bloodstream, and a treatment portion where people who test positive for cancer cell in their bloodstream may receive a or a .
- NCT04481113: Abemaciclib and Before Surgery for the Treatment of Hormone Receptor Positive Negative Breast Cancer. This phase I trial tests the side effects and best dose of abemaciclib and in treating patients with breast cancer that is positive for or progesterone receptors (hormone receptor positive [HR+]) and negative.
A number of other clinical trials for patients with breast cancer can be found here.
The following are studies looking at new treatments for people with TNBC.
- NCT03606967: Testing the Addition of an Individual Vaccine to Nab-Paclitaxel, Durvalumab and Tremelimumab and Chemotherapy in Patients With Triple Negative Breast Cancer. This study will look at how well the combination of chemotherapy, and when used with or without a vaccine made specifically for each patient.
- NCT04468061: Saci-IO TNBC: Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative TNBC. This early phase study is looking at how safe and effective Trodelvy with or without Pembrolizumab is in patients who have that has spread to other parts of the body.
- NCT04020575: Using a Type of Called CAR-T to Treat Triple-Negative Breast Cancer. This study will look at how safe and how well a type of treatment made from the patient's cancer works for treatment certain types of breast cancer.
- NCT03971409: Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Patients With IV or Unresectable, Recurrent (InCITe). This studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating TNBC that has recurred.
- NCT04491942: Testing a in Combination with Chemotherapy for Advanced . This study looks at how well a new drug called elimusertib works when combined with chemotherapy for treating people with triple-negative breast cancer and other advanced cancers.
- NCT04837209. Radiation, and in Triple Negative Breast Cancer (NADiR). This research study is looking to see whether the combination of Dostarlimab and plus Radiation Therapy (RT) is safe and effective in participants with triple negative breast cancer.
- NCT05081492: Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and (Pembrolizumab) for Triple-Negative Breast Cancer. This study is looking at the safety, side effects, and best dose of a drug called CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer. CF33-hNIS-antiPDL1 is a virus that is designed to attack and kill cancer cells.
A number of other clinical trials for treating patients with TNBC can be found here.