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 proteins found in some triple-negative breast cancers.

This page will help you understand what targeted therapies are available for triple-negative breast cancer, how they work, and which tests (or biomarkers) tell us who benefits from them.

Most targeted therapies for triple-negative breast cancers are FDA approved for cancers that have spread beyond the breast and nearby lymph nodes, and for breast cancers that cannot be removed surgically, or what your doctor might call unresectable. These treatments and other new therapies may be available for early-stage triple-negative breast cancer through clinical trials.

One treatment, olaparib (Lynparza), is approved to treat early-stage high-risk triple-negative breast cancer in people who test positive for a BRCA1 or BRCA2 mutation.

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.
• Trastuzumab deruxtecan (Enhertu) is approved to treat metastatic triple-negative breast cancers that have low amounts of the protein HER2 on the surface of the cancer cells. These cancers are considered HER2-low.

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. An ISH test produces a positive or negative result.

An IHC score of 3+ is considered HER2-positive. Cancers identified as triple-negative will have an IHC score of 0+, 1+, or 2+, as follows:

• 0+ - The cancer is HER2-negative and will not respond to medicines that target HER2.
• 1+ - The cancer is HER2-low.
• 2+ - This result is borderline and requires an ISH test to determine if the cancer is HER2-positive or HER2-low.

HER2-low is a new designation. 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 this medicine is an option for you.

Trastuzumab deruxtecan (Enhertu) is the only drug approved to treat metastatic HER2-low breast cancer. The clinical trial that led to the approval of this medicine for HER2-low breast cancer included mostly people with hormone-receptor positive breast cancer. The number of participants with triple-negative breast cancer was much smaller, but still significant. The benefit was seen in both groups.

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 35 percent of triple-negative breast cancers in Black people test positive for a BRCA1 mutation. In Caucasian people, 10-15 percent of triple-negative breast cancers test positive for a BRCA1 mutation. BRCA2 and other genetic 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.