Topic: Progress in the treatment of triple-negative breast cancer
During the December 2023 San Antonio Breast Cancer Symposium, Dr. Melinda Telli presented a summary of research that has led to better treatments for triple-negative breast cancer (TNBC). These treatments now include drugs called targeted therapies and immunotherapies for both early and late stages of TNBC. (Posted 3/19/24)
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RELEVANCE
Most relevant for: People with triple-negative breast cancer.
It may also be relevant for:
- people with triple negative breast cancer
Relevance: Medium-High
Research Timeline: Post Approval
What is this topic about?
This topic is about advances in the treatment of ().
Why is this topic important?
TNBC is a type of breast cancer that is aggressive and often difficult to treat. People who have an in are at especially high risk for TNBC compared with other types of breast cancer, although people with an inherited mutation in other genes are also at risk.
“Triple negative” means that the cancer lacks three tumor markers: (ER), progesterone (PR), and . Treatments that target these markers (for example, Herceptin, which targets HER2) are not options for patients with TNBC. Treatment for TNBC has been limited mainly to chemotherapy, but new treatment options have improved patient outcomes. At the 2023 San Antonio Breast Cancer Symposium, Dr. Telli talked about how these new treatments have positively changed the outlook for patients with TNBC.
Progress in the treatment of TNBC
PARP Inhibitors
PARP inhibitors are a type of that works by blocking a protein that the body uses to repair damage to . These drugs were initially developed to treat cancers in people with BRCA1 and mutations. Dr. Telli described research with the PARP inhibitors Lynparza () and () for patients with an inherited mutation in BRCA1 or BRCA2, including patients with TNBC.
Two studies of patients with advanced TNBC: OlympiAD (Lynparza) and EMBRACA (Talzenna) found these PARP inhibitors reduced cancer progression compared to standard chemotherapy.
The OlympiA study looked at using Lynparza just after surgery for people with TNBC. In this study, Lynparza increased both the time until cancer came back and overall survival (how long patients lived). Read more here and here.
Immunotherapy is a type of targeted therapy that helps the body’s immune system detect and attack cancer cells. Immunotherapies are used to treat many different cancer types. TNBC has a tumor marker called that is often used to determine if a patient will respond to immunotherapy. An immunotherapy drug called Keytruda (pembrolizumab) can now be used as a treatment in earlier and later stages of TNBC.
For patients with advanced TNBC, the KEYNOTE-355 study looked at adding Keytruda to chemotherapy as the first treatment. Researchers found that among patients whose tumors had high levels of PD-L1, this drug combination significantly increased both the time until cancer came back and survival when compared to using chemotherapy alone.
Researchers also found that Keytruda benefited patients with early-stage TNBC who were at high risk for recurrence due to the size of their cancer or the number of positive . In the KEYNOTE-522 study, Keytruda was added to chemotherapy before surgery ( treatment) and continued after surgery ( treatment). The addition of Keytruda to chemotherapy significantly increased the time until cancer came back. Read more about the approval of Keytruda for the treatment of early-stage breast cancer here.
Antibody Drug Conjugates
Antibody Drug Conjugates (ADCs) are drugs that combine two different types of molecules. A chemotherapy drug is linked to an antibody that delivers the chemotherapy directly to the cancer cells. Two ADCs are approved by the for patients with breast cancer: Trodelvy (sacituzumab govitecan or “SG”) and Enhertu (trastuzumab-deruxtecan or “T-DXd”). Dr. Telli covered the study results of these drugs involving TNBC that showed significant improvements over chemotherapy.
In the ASCENT study, researchers treated patients who had TNBC with either Trodelvy or chemotherapy. The risk of the cancer coming back was reduced by more than 50 percent among patients in the Trodelvy group compared with the patients in the chemotherapy group. Read more about Trodelvy here and here.
Enhertu is an ADC that delivers chemotherapy to tumor cells that have the HER2 protein. Previously, a breast tumor was designated as either or based on a cutoff value for the amount of HER2 protein. The DESTINY-Breast04 study looked at patients who had HER2 levels below this cutoff (traditionally considered HER2-negative). This new “HER2-low” subtype of breast cancer can include some patients who were originally told that they had TNBC. In HER2-low patients with metastatic breast cancer, Enhertu increased the time until cancer came back by about 50 percent compared with standard chemotherapy. Read more about HER2-low breast cancers and Enhertu here.
Chemotherapy
For people with TNBC, different ways of giving chemotherapy have also led to better patient outcomes.
In one study, researchers added carboplatin (a type of chemotherapy) to a standard chemotherapy treatment before surgery (neoadjuvant). They also showed that carboplatin increased the time until the cancer came back, as well as overall survival compared with standard chemotherapy alone. Patients who had the greatest benefit were mainly premenopausal and age 50 or younger.
While improving outcomes is a primary goal for treatment, being able to achieve this with fewer side effects was another theme of recent research. The NeoSTOP study compared a four-drug treatment (carboplatin/paclitaxel followed by doxorubicin/cyclophosphamide) to a two-drug treatment (docetaxel plus carboplatin) prior to surgery. Both groups had similar survival rates, but patients taking the two-drug treatment (docetaxel plus carboplatin) had fewer side effects.
Another study (CREATE-X) looked at patients with TNBC who still had some cancer (residual disease) after neoadjuvant chemotherapy. The addition of capecitabine to treatment after surgery increased the time until their cancer returned and overall survival. This study led to a change in how physicians treat this patient group.
Future Research
While great progress has been made in the treatment of TNBC, more work needs to be done. Other areas of future study include:
- Finding treatments with the same or better benefits with fewer side effects.
- Figuring out the best order of giving different treatments.
- After treatment of early TNBC, using circulating tumor DNA (a way to see if cancer is still present) to better understand if more treatment is needed.
- Identifying markers that can predict how well the drug will work or its side effects.
Recent Drug Approvals in TNBC
| Name of Drug | Cancer | Indication | Type of Drug | |
| Lynparza (olaparib) | Early-stage breast cancer at high risk for recurrence | Given for one year as after completion of neoadjuvant or and local treatment (surgery and, or radiation). | BRCA1 or BRCA2 inherited mutation* | |
| Metastatic | For treatment of patients who have previously received chemotherapy, or hormone therapy for patients with hormone receptor ()-positive disease | BRCA1 or BRCA2 mutation and HER2-negative* | ||
| Talzenna (talazoparib) |
Metastatic | For treatment of metastatic breast cancer | BRCA1 or BRCA2 mutation and HER2-negative* | PARP inhibitor |
| Keytruda (pembrolizumab) | Early-stage TNBC at high risk for recurrence | Before surgery, Keytruda is used with chemotherapy as neoadjuvant therapy. Following surgery, Keytruda is continued alone. | Triple-negative (, HER2-negative) |
Immune checkpoint inhibitor |
| 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 |
||
| 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 |
| Enhertu (fam-trastuzumab-deruxtecan-nxki) | Metastatic | Treatment for tumors that are HER2-low in people who received chemotherapy in the metastatic setting and whose cancer no longer responds to hormonal therapy | HER2-low* | Antibody-drug conjugate |
You can find more information on these treatments here.
Open Clinical Trials
The following studies are enrolling people with early-stage TNBC.
- NCT05629585: A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03). This study evaluates the safety and effectiveness of the investigational drug Dato-DXd given with or without durvalumab when compared with the combination capecitabine and/or pembrolizumab in people with stage 1-3 TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.
- NCT04584255: Treating Early-Stage BRCA, or PALB2-Associated Breast Cancer with a PARP Inhibitor () and Immunotherapy (Dostarlimab). This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with mutations.
- NCT03562637: Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC. The GLORIA study is a Phase III, trial investigating the use of the drug adagloxad simolenin (OBI-822) in combination with the drug OBI-821 for adjuvant treatment of patients with high-risk, early-stage TNBC.
- NCT05455658: STEMVAC in Patients With Early Stage Triple Negative Breast Cancer. This trial studies the effect of the STEMVAC vaccine to treat patients with patients with stage 2B-3 triple-negative breast cancer.
- NCT05929768: Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer. This study compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to the standard chemo-immunotherapy for the treatment of early-stage triple-negative breast cancer.
Several other clinical trials for patients with early-stage TNBC can be found here.
Updated: 05/28/2025
Open Clinical Trials
The following are studies looking at new treatments for people with metastatic TNBC.
- NCT03606967: Testing the Addition of an Individual Vaccine to Nab-Paclitaxel, Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer. This study evaluates how well the combination of chemotherapy, immunotherapy and targeted therapy when used with or without a vaccine made specifically for each patient.
- NCT04468061: Saci-IO TNBC: Randomized Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative Metastatic TNBC. This early phase study looks at the safety and effectiveness of Trodelvy with or without pembrolizumab for patients with TNBC that has spread to other parts of the body.
- NCT04020575: Using a Type of Immunotherapy Called CAR-T to Treat Metastatic Triple-Negative Breast Cancer. This study measures the safety and effectiveness of a treatment made from the patient's cancer when used for certain types of metastatic breast cancer.
- NCT03971409: Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Patients With Stage IV or Unresectable, Recurrent TNBC (InCITe). This project studies how well the combination of avelumab with liposomal doxorubicin works with or without binimetinib. It also studies the combination of avelumab with sacituzumab govitecan to treat metastatic TNBC that has recurred.
- NCT04837209. Radiation, Immunotherapy and PARP Inhibitor in Triple Negative Breast Cancer (NADiR). This research study is looking to see whether the combination of dostarlimab and niraparib plus radiation therapy is safe and effective for participants with metastatic triple-negative breast cancer.
- NCT05081492: Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer. This study identifies the safety, side effects, and best dose of a drug called CF33-hNIS-antiPDL1 (a virus that is designed to attack and kill cancer cells) for treating patients with metastatic triple negative breast cancer.
Several other clinical trials for treating patients with metastatic TNBC can be found here.
Updated: 02/23/2024
Peer Support
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:
Updated: 05/07/2024