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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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Progress in the treatment of triple-negative breast cancer
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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

Relevance Rating Details


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

*Studies included patients with

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

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What are my treatment options for ?
  • Was my tumor tested for using a test that measures HER2-low? If yes, what was the score? If not, can it be tested now?
  • What side effects can I expect from treatment?

Guidelines
Guidelines

National Comprehensive Cancer Network (NCCN) has guidelines for treatment of TNBC, which includes the following:

  • Genetic testing:
    • Everyone who is diagnosed with , regardless of their age should have genetic counseling and testing. 
  • Treatment for TNBC:
    • For small tumors (0.5 cm or smaller) with no positive , chemotherapy is recommended only 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 larger than 1.0 cm,  is recommended.  
    • For  2 or  3  in people who are at high risk for recurrence, pembrolizumab (Keytruda) in combination with chemotherapy followed by pembrolizumab is recommened.
    • For people with an inherited or mutation who are at high risk for recurrence, consider olaparib for 1 year after chemotherapy is completed. 
    • For people with remaining cancer after chemotherapy, capecitabine is recommended.  
    • For postmenopausal, node-negative patients who are at high risk for recurrence, or postmenopausal node-positive patients, consider bisphosphonate treatment for 3-5 years. 

Updated: 02/23/2024

Guidelines
Guidelines

National Comprehensive Cancer Network (NCCN) guidelines for treatment of advanced or TNBC includes the following:

  • Genetic testing:
    • All people diagnosed with at any age meet guidelines for genetic counseling and testing. 

The NCCN lists the following as preferred treatments for TNBC:

  • therapy:
    • For people with an inherited or mutation: (Lynparza) or (). 
    • For people without an inherited or mutation: chemotherapy. 
  • Second-line therapy:
    • For people with but who test HER2-low: fam-trastuzumab deruxtecan-nxki (Enhertu).
    • For people with who are not HER2-low: sacituzumab govitecan (Trodelvy) or chemotherapy.
  • Third -ine or higher therapy: 
    • The NCCN recommends based on testing.

Updated: 02/23/2024

Open Clinical Trials
Open Clinical Trials

The following are studies enrolling people with , .  

A number of other clinical trials for patients with TNBC can be found here.

Updated: 02/22/2024

Open Clinical Trials
Open Clinical Trials

The following are studies looking at new treatments for people with TNBC.  

A number of other clinical trials for treating patients with TNBC can be found here.

Updated: 02/23/2024

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 05/07/2024

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