Targeted therapy for triple-negative breast cancer

Targeted therapies, a type of systemic or full-body cancer treatment, work by targeting features present on cancer cells. Until recently, chemotherapy was the only systemic treatment option for triple-negative breast cancer. Today there are treatments available that target these cancers in different ways.

This page will help you understand the targeted therapies available for triple-negative breast cancer and how they work.

Antibody-drug conjugates

An antibody-drug conjugate, or ADC, is a treatment that pairs a powerful chemotherapy medicine with a targeted therapy. The targeted therapy directs the medicine to the cancer cells, so the chemotherapy medicine can be delivered to the insides of the cells. This helps limit the side effects of chemotherapy on healthy cells.

Two ADCs are approved to treat metastatic triple-negative breast cancer. Both treatments deliver chemotherapy through a target, and both are given by vein. The proteins they target, and the chemotherapy used, are different.

• Sacituzumab govetican (Trodelvy) is approved for all metastatic triple-negative breast cancers. It targets a protein common to triple-negative breast cancers, called Trop-2, and delivers the chemotherapy drug SN-38. Sacituzumab govetican is recommended by the National Comprehensive Cancer Network as a first treatment for people with metastatic TNBC. For people whose metastatic TNBC has a high level of the PD-L1 protein, NCCN recommends adding pembrolizumab (Keytruda) with sacituzumab govetican as a first treatment. FDA approval for these uses is in process.
• Trastuzumab deruxtecan (Enhertu) is approved to treat metastatic breast cancers that are confirmed to have low or trace amounts of the protein HER2 on the surface of the cancer cells. These cancers are considered HER2-low or HER2-ultralow.

Two types of laboratory tests are used to determine the HER2 status of a cancer. Immunohistochemical (IHC) testing measures the amount of HER2 on the cancer cells. A FISH test produces a positive or negative result.

• An IHC score of 3+: The cancer is HER2-positive.
• An IHC score of 0: The cancer is HER2-negative and will not respond to medicines that target HER2.
• An IHC score of 0 with very small amounts of HER2 on the cell surface: If the cancer is metastatic, your doctor may consider the cancer to be HER2-ultralow.
• An IHC score of 1+: In early-stage breast cancer, a 1+ score is usually considered to be HER2-negative. Doctors may consider metastatic breast cancer with a 1+ score to be HER2-low.
• An IHC score of 2+: This result is borderline and requires a FISH test to confirm HER2 status.

HER2-low and HER2-ultralow are newer designations. Trastuzumab deruxtecan (Enhertu) is the only drug approved to treat metastatic HER2-low and HER2-ultralow breast cancer. If you have metastatic breast cancer that was previously identified as HER2-negative, talk with your doctor about the results of your IHC test. Ask about the score and whether trastuzumab deruxtecan is an option for you.

Immunotherapy

Immunotherapy helps your own immune system destroy cancer cells. There is one immunotherapy called pembrolizumab (Keytruda) that is FDA approved to treat triple-negative breast cancer.

• Pembrolizumab is approved to treat early-stage triple-negative breast cancer that has a high risk of recurrence. In these cancers, pembrolizumab is given in combination with chemotherapy before surgery (neoadjuvant treatment). After surgery, it is given alone.

• Pembrolizumab is also approved to treat breast cancer that is metastatic or that can’t be removed with surgery and tests positive for a protein called PD-L1. For these cancers, pembrolizumab is given in combination with chemotherapy as a first treatment. 

PARP inhibitors

PARP inhibitors are FDA approved to treat metastatic and high-risk, early-stage, triple-negative breast cancer in people who were born with an inherited BRCA1 or BRCA2 gene mutation. These mutations can increase the risk of breast cancer, including triple-negative breast cancer.

• About 20 to 35% of Black people with triple-negative breast cancers test positive for an inherited BRCA1 gene mutation.
• About 10 to 15% of Caucasian people with triple-negative breast cancers test positive for an inherited BRCA1 gene mutation.
• BRCA2 and other inherited gene mutations can also increase the risk of triple-negative breast cancer.

PARP inhibitors stop an enzyme in the body, poly (ADP-ribose) polymerase, or PARP, from repairing cancer cell DNA. Cancer cells in people with BRCA mutations already have a hard time repairing their DNA. PARP inhibitors make it even harder and can cause the cancer cells to die.

There are two PARP inhibitors approved to treat metastatic breast cancers caused by an inherited BRCA genetic mutation. They are olaparib (Lynparza) and talazoparib (Talzenna). Olaparib is also approved to treat high-risk early-stage breast cancers. Both medicines are taken as a pill.

These treatments may be an option if you:

• Were born with a BRCA1 or BRCA2 mutation
• Have breast cancer that is either triple-negative or hormone-receptor positive and HER2-negative
• Have been treated with chemotherapy in the past, either for early-stage or metastatic breast cancer

Genetic testing for an inherited mutation can confirm whether you have an BRCA mutation. This is done using a blood, saliva, or cheek-swab test. Genetic counseling and testing are often recommended if you have a strong family history of breast or ovarian cancer, a personal history of breast cancer at a young age, or a confirmed BRCA1 or BRCA2 mutation in your family. There are also other testing eligibility factors you and your doctor may consider. Visit the Genetic testing and family risk page to learn more.