Risk Management & Treatment

Biomarkers, targeted and immunotherapies for breast cancer

This section covers the following topics:


Biomarker testing for treatment selection

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) 
  • Her2 


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:

  • FoundationOne
  • MSK-IMPACT


Genetic tests for inherited mutations for treatment selection

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. 


Tumor biomarker tests for prognosis 

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™ 
  • MammaPrint™ 
  • Prosigna™ 


PARP inhibitors 

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 

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. 


Other targeted therapies

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
Herceptin
(trastuzumab) 
Early stage The treatment of Her2-positive breast cancer Her2 overexpression (Her2-positive) Antibody targeting Her2 receptors
  
Perjeta (pertuzumab)
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
(ER/PR-negative, Her2-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
Kadcyla
(trastuzumab emtansine)
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
Kadcyla
(trastuzumab emtansine)
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)
Afinitor
(everolimus)
Metastatic  Combined with Aromasin (exemestane) for postmenopausal women with advanced breast cancer which progressed with Femara (letrozole) or Arimidex (anastrozole) ER/PR-positive
and Her2-negative
MTOR inhibitor (type of kinase inhibitor)
Piqray
(alpelisib)
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
Kinase inhibitor
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
and Her2-negative
CDK4/6 inhibitor
Metastatic Combined with Faslodex (fulvestrant) as treatment in  women whose disease progressed following endocrine therapy. ER/PR-positive and Her2-negative CDK4/6 inhibitor
Ibrance
(palbociclib)
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
Kisqali
(ribociclib)
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
Talzenna
(talazoparib)
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)
PD-L1-positive
Immune checkpoint inhibitor
paying-for-service

The majority of public and private health insurance plans are required to cover cancer diagnosis and treatment; copays, coinsurance and deductibles often apply. Patient costs and coverage for specific doctors, facilities or treatments may vary based on your health plan. Visit our section on Insurance and Paying for Care: Treatment  for more information, links to sample appeal letters and other resources. 

Some pharmaceutical companies and laboratories have assistance programs that help cover the cost for their medications, tumor testing or genetic testing for an inherited mutation: 

Other resources:

  • The American Cancer Society provides information and resources on covering the cost of cancer care. Public assistance, such as Medicaid may be available if you are ineligible for other programs. 
  • The Lazarex Foundation provides financial support for people participating in clinical trials. Their programs include financial support for people with advanced cancer who need to travel to participate in a clinical trial. 
  • Susan G. Komen partners with Cancercare to offer the Komen Treatment Assistance Program which bridges the gap for underserved individuals who are actively undergoing breast cancer treatment.
  • Needy Meds: Assistance programs to help patients with cost of medications and other healthcare.
  • Triage Cancer offers tools and resources to help individuals cope with the financial aspects of a cancer diagnosis.
clinical-trials

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

Advanced solid tumors of any type, including breast cancer

Last updated August 30, 2021