Biomarkers, targeted and immunotherapies for breast cancer
This section covers the following topics:
- Tumor biomarker testing for treatment selection
- Genetic testing for inherited mutations for treatment selection
- Tumor biomarker testing for prognosis
- PARP inhibitors
- Other targeted therapy
Biomarker 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
Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker 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 Biomarker Testing section for more information.
ER, PR and HER2
After breast cancer tissue is removed by surgery or biopsy, it is standard of care to test all breast cancers for three common biomarkers:
- estrogen receptors (ER)
- progesterone receptors (PR)
Biomarkers for Advanced Breast Cancer
For people with advanced breast cancer, additional biomarker 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 biomarker test for a specific targeted therapy is sometimes called a companion diagnostic test. Some tests look for only one biomarker at a time. Examples of single biomarker tests for breast cancer include:
- PIK3CA: Testing for this gene in advanced ER-positive, Her2-negative breast cancer can help identify people most likely to respond to the medication PIQRAY (alpelisib).
- PD-L1: Testing for the PD-L1 protein can help identify people with advanced triple-negative breast cancer (TNBC) who are most likely to respond to the immunotherapy drugs Tecentriq (atezolizumab) and Keytruda (pembrolizumab).
Other tests may search for many biomarkers within the same test. Often these 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 biomarker tumor tests for breast cancer include:
Genetic testing for an inherited mutation may be used to guide treatment selection for people diagnosed with breast cancer.
- People with advanced breast cancer who test positive for an inherited BRCA1 or BRCA2 mutation may benefit from treatments known as PARP inhibitors. Two PARP inhibitors—Lynparza and Talzenna—are approved as targeted therapy for treating advanced breast cancer in people with a BRCA1 or BRCA2 mutation.
- 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 early stage 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 DNA. They were initially developed to treat cancers in people with an inherited gene mutation BRCA1 or BRCA2 mutation. Two PARP inhibitors have received FDA-approval as targeted therapy for treating people with metastatic or locally advanced breast cancer in people with an inherited BRCA mutation.
- Lynparza (olaparib)
- Talzenna (talazoparib)
Additionally, Lynparza may be used to treat early stage breast in people with an inherited BRCA inherited mutation who are at high risk for recurrence.
Research is ongoing to learn if PARP inhibitors are affective for treating breast cancer in other situations, including:
- people with an inherited mutation in a different gene that repairs DNA damage (for example: PALB2, ATM or CHEK2).
- people who do not have an inherited gene mutation, but their tumor tested positive for an acquired mutation in a gene that repairs DNA damage.
Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. Immune checkpoint inhibitors are a type of immunotherapy 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 triple-negative breast cancer that is metastatic or locally recurrent and unresectable that tests positive for a biomarker called PD-L1.
- Keytruda is approved for the treatment of early-stage triple-negative breast cancer that is at high risk for recurrence. In this setting, Keytruda is used along with chemotherapy as neoadjuvant therapy before surgery. Following surgery, Keytruda is continued alone.
See our Immunotherapy section for more information.
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 biomarker testing can help doctors identify the patients most likely to benefit from a targeted therapy. Common targeted therapies used in breast cancer include:
- Her2-positive breast cancers are often treated with drugs that target the Her2 protein. Common anti-Her2 therapies include Herceptin (trastuzumab), Perjeta (pertuzumab) and Tukysa (tucatinib) and Phesgo (pertuzumab, trastuzumab and hyaluronidase).
- People with ER/PR-positive 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 FDA approved for people who have advanced, ER/PR-positive breast cancer who test positive for a tumor biomarker 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 stage||Indication||Biomarker||Type of agent|
|Early stage||The treatment of Her2-positive breast cancer||Her2 overexpression (Her2-positive)||Antibody targeting Her2 receptors|
|Locally advanced, inflammatory or early stage||Combined with Herceptin (trastuzumab) and docetaxel as treatment before surgery (neoadjuvant)||Her2 overexpression (Her2-positive)||Antibody targeting Her2 receptors|
|Phesgo (pertuzumab, trastuzumab combined injection)||Early stage||
Before surgery (neoadjuvant) for tumors larger than 2 cm or node-positive or after surgery (adjuvant treatment) for early breast cancer that has a high likelihood of coming back
|Her2 overexpression (Her2-positive)||Antibody targeting Her2 receptors|
|Keytruda (pembrolizumab)||Early stage TNBC at high risk for recurrence||Before surgery Keytruda is used along with chemotherapy as neoadjuvant therapy. Following surgery, Keytruda is continued alone.||Triple-negative
|Immune checkpoint inhibitor|
|Lynparza (olaparib)||Early stage breast cancer at high risk for recurrence||Given for one year as maintenance therapy after completion of neoadjuvant or adjuvant chemotherapy and local treatment (surgery and, or radiation).||BRCA1 or BRCA2 inherited mutation||PARP inhibitor|
|Early stage||Adjuvant treatment of patients with early breast cancer who still have disease after neoadjuvant taxane and treatment with Hercptin||Her2 overexpression (Her2-positive)||Antibody targeting Her2 receptors|
|Metastatic||For patients who previously received Herceptin and chemotherapy, separately or in combination. Patients should have either received therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy||Her2 overexpression (Her2-positive)||Antibody targeting Her2 receptors|
|Tukysa (tucatinib)||Metastatic||In combination with Herceptin (trastuzumab) to treat cancer which has progressed after at least one prior treatment with an anti-HER2 treatment in the metastatic setting||Her2 overexpression (Her2-positive)||Kinase inhibitor|
|Trodelvy (sacituzumab govitecan-hziy)||Metastatic||For metastatic breast cancer that progressed, recurred or did not respond to at least two previous lines of treatment||Triple-negative (ER/PR-negative, Her2-negative)||Antibody-drug conjugate (chemotherapy attached to antibody found in TNBC)|
|Metastatic||Combined with Aromasin (exemestane) for postmenopausal women with advanced breast cancer which progressed with Femara (letrozole) or Arimidex (anastrozole)||ER/PR-positive
|MTOR inhibitor (type of kinase inhibitor)|
|Metastatic||Combined with Faslodex (fulvestrant) as treatment in men or post-menopausal women who progressed on or after treatment with hormone therapy.||ER/PR-positive
and Her2-negative and PIK3CA-positive
|Verzenio (abemaciclib)||Metastatic||Used alone to treat men or women with breast cancer that has progressed after treatment with hormone therapy and chemotherapy in the metastatic setting.||ER/PR-positive
|Metastatic||Combined with Faslodex (fulvestrant) as treatment in women whose disease progressed following endocrine therapy.||ER/PR-positive and Her2-negative||CDK4/6 inhibitor|
|Metastatic||Combined with an aromatase inhibitor as treatment of
advanced cancer as initial hormone therapy in postmenopausal women or in men
|ER/PR-positive and Her2-negative||CDK4/6 inhibitor|
|Metastatic||Combined with Faslodex (fulvestrant) as treatment in postmenopausal women or in men whose disease progressed following endocrine therapy||ER/PR-positive and Her2-negative||CDK4/6 inhibitor|
|Metastatic||Combined with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women as initial hormone based therapy||ER/PR-positive and Her2-negative||CDK4/6 inhibitor|
|Metastatic||Combined with Faslodex (fulvestrant) for the treatment of postmenopausal women, as initial hormone based therapy.||ER/PR-positive and Her2-negative||CDK4/6 inhibitor|
|Lynparza (olaparib)||Metastatic||For treatment of patients who have previously received chemotherapy, or hormone therapy for patients with hormone receptor (HR)-positive disease||BRCA1 or BRCA2 mutation and Her2-negative||PARP inhibitor|
|Metastatic||For treatment of metastatic breast cancer||BRCA1 or BRCA2 mutation and Her2-negative||PARP inhibitor|
|Keytruda (pembrolizumab)||Metastatic||Combined with chemotherapy for treatment of locally recurrent unresectable or metastatic triple negative breast cancer||Triple-negative (ER/PR-negative and Her2-negative)
|Immune checkpoint inhibitor|
The following clinical trials are focused on targeted or immunotherapies for people with an inherited mutation who have been diagnosed with breast cancer.
Breast cancer specific
- NCT03964532: TALAVE: A Pilot Trial of Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer. TALAVE is a study for patients who have advanced or metastatic breast cancer to look at whether giving talazoparib alone followed by talazoparib with avelumab is a safe and effective treatment.
- NCT03344965: A Phase 2 Study of Olaparib Monotherapy in Metastatic Breast Cancer Patients with Germline or Somatic Mutations in DNA Repair Genes (Olaparib Expanded). Olaparib (Lynparza) is a type of treatment known as a PARP inhibitor, which is approved for metastatic breast cancer in people with a BRCA mutation. This study is looking at how well olaparib works in people with a BRCA or other mutation.
- NCT03344965: A Phase 2 Study of Olaparib Monotherapy in Metastatic Breast Cancer Patients with Germline or Somatic Mutations in DNA Repair Genes (Olaparib Expanded). This study is looking at how well olaparib works in people with metastatic breast cancer and any of the following mutations (either inherited or found on tumor testing) : ATM, ATR, BARD1, BRIP1 (FANCJ), CHEK2 , FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD50, RAD51C,
- NCT02401347: Talazoparib Beyond BRCA (TBB) Trial. People with an inherited mutation who have metastatic triple-negative breast cancer may qualify for this study. This study is looking at how well the PARP inhibitor talazoparib works in people with the following mutations (either inherited or found on tumor testing) : PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, Rad51c, Rad51d, MRE11, ATR, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, plus other HR-related genes at the discretion of the primary investigators.
- NCT03911973: Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers. This study is designed to determine efficacy of gedatolisib in combination with talazoparib in advanced HER2-negative breast cancer that is triple negative or caused by a BRCA1/2 mutation.
- Breast Cancer Treatment in Women with PALB2 Mutations. The PALB2 Study is an international research study to better understand breast cancer treatment among women with a PALB2 gene mutation. Participants are asked to complete online or paper study questionnaires (every two years for 10 years) and share their family history, medical, and genetics records.
Advanced solid tumors of any type, including breast cancer
- NCT03565991: A Phase II Study to Evaluate the Safety and Anti-tumor Activity of Avelumab in Combination with Talazoparib in Patients with a BRCA or ATM Mutation. This study is looking at the safety and effectiveness of the combination of an immunotherapy (known as Avelumab) and a PARP inhibitor (known as Talazoparib) is for treating patients with locally advanced or metastatic solid tumors who have an inherited mutation in ATM, BRCA1 or BRCA2.
- NCT04171700: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (LODESTAR). This study is evaluating the response of rucaparib in patients with advanced cancers and with deleterious mutations (either inherited or found on tumor testing) in Homologous Recombination Repair (HRR) genes, including: BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B.