Topic: Progress in the treatment of triple-negative breast cancer
Summary
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?
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 compared with other types of breast cancer, although people with an 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 ) are not options for patients with . Treatment for 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 .
Progress in the treatment of
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 and mutations. Dr. Telli described research with the PARP inhibitors Lynparza () and () for patients with an in or , including patients with .
Two studies of patients with advanced TNBC: OlympiAD (Lynparza) and EMBRACA () 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.
is a type of that helps the body’s immune system detect and attack cancer cells. Immunotherapies are used to treat many different cancer types. has a tumor marker called that is often used to determine if a patient will respond to . An drug called Keytruda (pembrolizumab) can now be used as a treatment in earlier and later stages of .
For patients with advanced , 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 , 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 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 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 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 protein. Previously, a breast tumor was designated as either or based on a cutoff value for the amount of protein. The DESTINY-Breast04 study looked at patients who had levels below this cutoff (traditionally considered ). This new “HER2-low” subtype of breast cancer can include some patients who were originally told that they had . In HER2-low patients with 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 , 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 (). 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 who still had some cancer (residual disease) after 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 , 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 , using circulating tumor (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
| Name of Drug | Cancer | Indication | Type of Drug | |
| Lynparza () | breast cancer at high risk for recurrence | Given for one year as after completion of or and local treatment (surgery and, or radiation). | or inherited mutation* | |
| For treatment of patients who have previously received chemotherapy, or hormone therapy for patients with hormone receptor ()-positive disease | or mutation and HER2-negative* | |||
() |
For treatment of breast cancer | or mutation and HER2-negative* | ||
| Keytruda (pembrolizumab) | at high risk for recurrence | Before surgery, Keytruda is used with chemotherapy as therapy. Following surgery, Keytruda is continued alone. | Triple-negative (, ) |
Immune checkpoint inhibitor |
| Combined with chemotherapy for treatment of locally recurrent unresectable or | Triple-negative ( and ) PD-L1-positive |
|||
| Trodelvy (sacituzumab govitecan-hziy) | For breast cancer that progressed, recurred or did not respond to at least two previous lines of treatment | Triple-negative (, ) | Antibody-drug conjugate | |
| Enhertu (fam-trastuzumab-deruxtecan-nxki) | Treatment for tumors that are HER2-low in people who received chemotherapy in the setting and whose cancer no longer responds to hormonal therapy | HER2-low* | Antibody-drug conjugate |
You can find more information on these treatments here.
What does this mean for me?
Although more work in this field is needed, these recently approved drugs have made a positive difference for some patients by delaying the progression of their cancer and helping them live longer.
If you have been diagnosed with , you may want to ask your doctor about newer treatment options. You may also want to ask if your cancer is “HER2-low,” which can help in determining the best treatment for you.
Reference:
Telli M. Recent advances in . San Antonio Breast Cancer Symposium, December 2023.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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posted 3/19/24
Guidelines
The National Comprehensive Cancer Network (NCCN) has guidelines for treatment of TNBC, which includes the following:
- Genetic testing:
- All people diagnosed with at any age meet guidelines for genetic counseling and testing.
- Treatment for TNBC:
- For small tumors (0.5 cm or smaller) with no positive , the guidelines don't recommend chemotherapy except for patients at high risk for recurrence.
- For small tumors (larger than 0.5 cm) with 1 positive lymph node or tumors between 0.6 and 1.0 cm, consider .
- For tumors that are larger than 1.0 cm, is recommended.
- For 2 or 3 in people who are at high risk for recurrence, the panel recommends pembrolizumab (Keytruda) in combination with chemotherapy followed by pembrolizumab.
- For people with an inherited or mutation who are at high risk for recurrence, consider olaparib for one year after chemotherapy is completed.
- For people with remaining cancer after chemotherapy, the guidelines recommend capecitabine.
- For post-menopausal, node-negative patients who are at high risk for recurrence, or post-menopausal node positive patients, consider bisphosphonate treatment for 3-5 years.
Updated: 02/23/2024
Guidelines
The National Comprehensive Cancer Network (NCCN) has guidelines for treatment of TNBC, which includes the following. The guidelines for advanced or TNBC includes the following:
- Genetic testing:
- All people diagnosed with at any age meet guidelines for genetic counseling and testing.
NCCN lists the following as preferred treatments for TNBC:
- therapy:
- For people with an inherited or mutation, the guidelines recommend (Lynparza) or ().
- For people without an inherited or mutation, the guidelines recommend chemotherapy.
- Second-line therapy:
- For people with but who test HER2-low, the guidelines recommend Fam-trastuzumab deruxtecan-nxki (Enhertu).
- For people with who are not HER2-low, the guidelines recommend Sacituzumab govitecan (Trodelvy) or chemotherapy.
- Third line or higher:
- NCCN recommends based on testing.
Updated: 02/23/2024
Related resources
The following organizations have resources related to breast cancer.
- FORCE related resources:
- Information: Breast cancer screening and prevention
- Information: Breast cancer treatment
- Personalized portal: Breast cancer
- XRAY category: Breast cancer
- XRAY category: breast cancer
- Video playlist: Breast cancer
- Blogs: Breast cancer
- General breast cancer resources:
- breast cancer resources:
- Male breast cancer resources:
- Resources for Black, Indigenous and People of Color:
Updated: 06/28/2023
Open Clinical Trials
The following are studies enrolling people with , .
- NCT05629585: A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With I-III Without Pathological Complete Response Following Therapy (TROPION-Breast03). The study will look at how safe and effective the investigational drug Dato-DXd is with or without durvalumab when compared with the combination capecitabine and/or pembrolizumab in people with I to III who have residual invasive disease in the breast and/or axillary at surgical resection following systemic therapy.
- NCT04584255: Treating BRCA, or PALB2-Associated Breast Cancer with a () and (Dostarlimab). This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with mutations.
- NCT04674306: Therapy With an Alpha-lactalbumin Vaccine in . The purpose of this study is to determine the safety as well as the most effective dose of the alpha-lactalbumin vaccine (aLA breast cancer vaccine) to treat patients with non-metastatic triple negative breast cancer.
- NCT03562637: Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Treatment of Patients With Globo H Positive . The GLORIA study is a Phase III, trial looking at the use of the drug adagloxad simolenin (OBI-822) in combination with the drug OBI-821 in the treatment of patients with high-risk TNBC.
- NCT05455658: STEMVAC in Patients With Early Triple Negative Breast Cancer. This trial studies the effect of a vaccine (STEMVAC) to treat patients with patients with IB-III triple negative breast cancer.
- NCT05929768: Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Triple Negative Breast Cancer. This study compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to usual chemo-immunotherapy for the treatment of triple negative breast cancer.
A number of other clinical trials for patients with TNBC can be found here.
Updated: 02/22/2024
Open Clinical Trials
The following are studies looking at new treatments for people with TNBC.
- NCT03606967: Testing the Addition of an Individual Vaccine to Nab-Paclitaxel, Durvalumab and Tremelimumab and Chemotherapy in Patients With Triple Negative Breast Cancer. This study will look at how well the combination of chemotherapy, and when used with or without a vaccine made specifically for each patient.
- NCT04468061: Saci-IO TNBC: Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in PD-L1-negative TNBC. This early phase study is looking at how safe and effective Trodelvy with or without Pembrolizumab is in patients who have that has spread to other parts of the body.
- NCT04020575: Using a Type of Called CAR-T to Treat Triple-Negative Breast Cancer. This study will look at how safe and how well a type of treatment made from the patient's cancer works for treatment certain types of breast cancer.
- NCT03971409: Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Patients With IV or Unresectable, Recurrent (InCITe). This studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating TNBC that has recurred.
- NCT04837209. Radiation, and in Triple Negative Breast Cancer (NADiR). This research study is looking to see whether the combination of Dostarlimab and plus Radiation Therapy (RT) is safe and effective in participants with triple negative breast cancer.
- NCT05081492: Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and (Pembrolizumab) for Triple-Negative Breast Cancer. This study is looking at the safety, side effects, and best dose of a drug called CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer. CF33-hNIS-antiPDL1 is a virus that is designed to attack and kill cancer cells.
A number of other clinical trials for treating patients with 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: 11/29/2022