The Who, What, Where, When and Sometimes, Why.

Emerging Areas in Metastatic Breast Cancer Treatment

This is a promising time in metastatic breast cancer research. Many new treatments for metastatic breast cancer are under study and treatment is improving. Most of these new treatments are drug therapies.

Findings from clinical trials will determine whether or not these new treatments become a part of the standard of care for metastatic breast cancer.

Some treatments may even go on to be used for early-stage breast cancer care.

Learn about clinical trials.

HER2-targeted therapies

About 10-20 percent of breast cancers have high amounts of a protein called HER2 on the surface of the cancer cells (called HER2-positive breast cancer) [22-23]. The HER2 protein is important for cancer cell growth.

HER2-targeted therapies are designed to treat HER2-positive breast cancers. Find a complete list of HER2-targeted therapies FDA-approved for the treatment of metastatic breast cancer.

Other HER2-targeted drugs for the treatment of metastatic breast cancer are under study.

Learn about HER2-targeted therapies and early breast cancer treatment.

HER2-targeted therapies and HER2-low metastatic breast cancer

The HER2-targeted therapy trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan) is under study for use in the treatment of metastatic breast cancers that have low, but detectable, levels of HER2 expression [111]. These are called HER2-low breast cancers.

Immunohistochemistry (IHC) is a test which detects the amount of HER2 protein on the surface of the cancer cells. The results of an IHC test are used to show HER2 status. An IHC score of 1 or 2 shows a tumor is HER2-low.

Results of an IHC test

Score is 0

Tumor is HER2-negative

Score is 1+ or 2+

Tumor is HER2-low

Score is 3+

Tumor is HER2-positive

Selective estrogen receptor degraders (SERDs)

Selective estrogen receptor degraders (SERDs) are a type of hormone therapy. These anti-estrogen drugs bind to the estrogen receptor in a tumor cell. They cause the receptor to be broken down by the cell.

Other SERDs are under study for the treatment of metastatic breast cancer, including several drugs that are pills [81].

Selective androgen receptor agonists

Androgens are hormones produced in the body that are important in sexual development in both men and women. Some cancer cells have special proteins called androgen receptors. When androgens attach to androgen receptors, the cancer cells with these receptors grow.

Selective androgen receptor agonists are drugs that slow the growth of breast cancers that have androgen receptors.

The selective androgen receptor agonist enobosarm (Ostarine) is under study for the treatment of metastatic breast cancers that are estrogen receptor-positive and have androgen receptors.

Cyclin-dependent kinase 7 (CDK7) inhibitors

CDK7 is an enzyme important in cell growth. CDK7 inhibitors are drugs designed to interrupt the growth of cancer cells.

The CDK7 inhibitor samuraciclib in combination with hormone therapy is under study for the treatment of metastatic breast cancer.

PI3 kinase inhibitors

PI3 kinase is an enzyme important in cell growth. The PIK3CA gene helps control PI3 kinase enzyme activity.

Some breast cancers have a mutation in the PIK3CA gene (this gene mutation is in the genes of breast cancer, not the person). This mutation can affect PI3 kinase and cause the tumor to grow.

PI3 kinase inhibitors are drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells.

The PI3 kinase inhibitor alpelisib (Piqray) is FDA-approved to treat some metastatic breast cancers that have a mutation in the PIK3CA gene and are hormone receptor-positive and HER2-negative.

Other PI3 kinase inhibitors and other drugs that treat metastatic breast cancers with a PIK3CA tumor gene mutation are under study.

Immunotherapy

Immunotherapy drugs help the body’s immune system attack cancer cells. They are used to treat many cancers including melanoma, lung cancer, bladder cancer and kidney cancer.

Some immunotherapy drugs may be helpful in treating certain breast cancers.

Researchers are studying how to identify the best biomarkers for immunotherapy.

Checkpoint inhibitors are the most widely used type of immunotherapy drugs. These drugs “take the brakes off” the natural factors that limit how the immune system can control tumor cells.

The checkpoint inhibitor immunotherapy drug pembrolizumab (Keytruda) is FDA-approved for the treatment of metastatic triple negative breast cancers that express (have a lot of) programmed cell death protein 1 (PD-L1).

Other immunotherapy drugs are under study for the treatment of metastatic breast cancer.

Learn about the immunotherapy drug pembrolizumab and early breast cancer treatment.

Atezolizumab (Tecentriq)

Early data showed the checkpoint inhibitor immunotherapy drug atezolizumab benefited some women with metastatic breast cancer [50]. So, this drug was given accelerated FDA approval in 2019. However, the manufacturer withdrew its application for full FDA approval in August 2021.

If you’ve been taking atezolizumab for metastatic breast cancer, talk with your health care provider about your treatment options.

Atezolizumab remains FDA-approved for use in other cancers.

Trop-2 antibody-drug conjugates

Special antibody drugs are designed to target certain cancer cells. Antibody-drug conjugates are a combination of an antibody therapy and a chemotherapy drug. Combining these into one drug allows the targeted delivery of the chemotherapy to specific cancer cells.

Some breast cancers express Trop-2. This means they have cells with higher levels of the protein Trop-2 than other breast cancers. Triple negative breast cancers tend to express Trop-2.

Sacituzumab govitecan (Trodelvy) is an FDA-approved Trop-2 antibody-drug conjugate used to treat metastatic triple negative breast cancers.

Sacituzumab govitecan is under study for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancers [112].

Other Trop-2 antibody-drug conjugates are under study for the treatment of metastatic breast cancer.

PARP inhibitors

Poly(ADP-ribose) polymerase (PARP) inhibitor drugs are under study for many types of cancer, including breast cancer.

PARP is an enzyme involved in DNA repair. Some chemotherapy drugs damage tumor DNA. PARP inhibitors work to stop PARP from repairing tumor DNA to help the chemotherapy kill the cancer cells.

PARP inhibitors are currently only used to treat metastatic breast cancer in people who have a BRCA1 or BRCA2 inherited gene mutation. BRCA1/2-related breast cancers have problems repairing tumor DNA. These breast cancers seem to be sensitive to DNA damage caused by PARP inhibitors. Treating BRCA1/2-related breast cancers with a PARP inhibitor makes it even harder for the breast cancer to repair itself, leading to tumor cell death.

The PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) are FDA-approved for the treatment of HER2-negative metastatic breast cancer in people who have a BRCA1/2 inherited gene mutation.

Study findings suggest women with metastatic breast cancer who have a PALB2 inherited gene mutation may also benefit from treatment with olaparib [77].

Other PARP inhibitors, such as veliparib, are under study for the treatment of metastatic breast cancer [78].

Learn about the PARP inhibitor olaparib and early breast cancer treatment.

G-quadruplex stabilizers

The G-quadruplex stabilizer drug pidnarulex is under study for the treatment of metastatic breast cancer in people who have a BRCA1, BRCA2 (BRCA1/2) or PALB2 inherited gene mutation.

BRCA1/2-related and PALB2-related breast cancers have problems repairing DNA.
Pidnarulex targets these DNA repair defects in the cells of BRCA1/2-related metastatic breast cancers. It may cause breaks in tumor DNA, leading to cancer cell death.

Histone deacetylase (HDAC) inhibitors

Histone deacetylase (HDAC) inhibitors are drugs that target HDAC enzymes. These enzymes are important for some cell functions.

HDAC inhibitors can block HDAC enzymes on the cancer growth pathway. This may slow tumor growth and lead to tumor cell death.

Some HDAC inhibitors, such as entinostat and tucidinostat, are under study for the treatment of metastatic breast cancer [79]. However, most findings to date show no benefit.

Anti-angiogenesis drugs

Anti-angiogenesis drugs block the growth of new blood vessels (angiogenesis). Without a blood supply, the cancer can’t grow.

Although early data showed the anti-angiogenesis drug bevacizumab (Avastin) benefited some women with metastatic breast cancer, longer-term follow-up data did not confirm these findings. In 2011, the FDA withdrew approval for the use of bevacizumab in the treatment of metastatic breast cancer [80].

However, other anti-angiogenesis drugs are still under study for the treatment of metastatic breast cancer.

Bevacizumab remains FDA-approved for use in other cancers.

Emerging methods of checking treatment response

Tumors often develop resistance (stop responding) to drugs used to treat metastatic breast cancer.

New ways to monitor response to treatment are under study. 

Circulating tumor cells and circulating tumor DNA (liquid biopsies)

Circulating tumor cell levels can help predict survival for people with metastatic breast cancer [82-83].

The more circulating tumor cells in the blood, the more advanced the metastatic breast cancer tends to be.

Having more circulating tumor cells may also predict a lack of response to treatment.

Circulating tumor DNA is also under study for use in monitoring metastatic breast cancer and predicting treatment response [84-87].

Circulating tumor cell and circulating tumor DNA tests (sometimes called liquid biopsies) are not used today to guide treatment. This is because they haven’t been shown to offer benefit [4,88-91].

However, these methods are under study.  

Other uses of circulating tumor DNA in breast cancer treatment

If treatment with the drug alpelisib (Piqray) is being considered, circulating tumor DNA testing can be used to see if the cancer cells have a PIK3CA tumor gene mutation [4].

quote_icon

Komen Perspectives

Read our perspective on metastatic breast cancer.*

Learn More

Our commitment to research

At Susan G. Komen®, we are committed to saving lives by meeting the most critical needs in our communities and investing in breakthrough research to prevent and cure breast cancer. Our Research Program is an essential driving force for achieving this mission.

Since our inception in 1982, Komen has provided funding to support research grants that have greatly expanded our knowledge of breast cancer and helped us understand that breast cancer is not just a single disease but many diseases, unique to each individual.

To date, Komen has provided nearly $1.1 billion to researchers in 47 states, the District of Columbia and 24 countries to support research that has resulted in a better understanding of breast cancer; earlier detection; personalized, less invasive treatments for what was once a “one-treatment-fits-all” disease; and improvements in both quality of life and survival rates.

Learn more about our continuing investment in research and the exciting research that we are funding, because nothing would make us happier than ending breast cancer forever.

 

Clinical trials

After talking with your health care provider, we encourage you to consider joining a clinical trial for metastatic breast cancer.

If your medical center doesn’t offer clinical trials, you may want to get a referral to a cancer center that does.

 Susan G. Komen® Breast Care Helpline

If you or a loved one needs information or resources about clinical trials, call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email clinicaltrialinfo@komen.org.

The helpline offers breast cancer clinical trial education and support, such as:

  • Knowing when to consider a trial
  • How to find a trial
  • How to decide which trial is best
  • What to expect during a trial
  • Information about clinical trial resources

Se habla español.

Metastatic Trial Search

The Metastatic Trial Search is a web-based clinical trial matching tool that can help you find clinical trials that fit your needs.

Learn more about clinical trials for people with metastatic breast cancer and find a list of resources to help you find a clinical trial.  

 What is Susan G. Komen® doing?

Susan G. Komen® supported the Reagan-Udall Foundation and the Food and Drug Administration (FDA) in the development of the Expanded Access Navigator website.

Expanded Access (EA) is also known as “compassionate use.” It gives patients access to drugs before they have FDA approval. This may be needed when patients have no other treatment options and are not eligible for (or unable to participate in) a clinical trial.

The Expanded Access (EA) Navigator tool serves as a clearinghouse of information and resources to help patients and their doctors more easily access information that could impact treatment decisions. The EA Navigator explains what EA is, who may be eligible, how the request process works, as well as the regulatory and policy issues around EA.

The EA Navigator also contains pharmaceutical companies’ EA policies. The open EA programs are listed on the National Institutes of Health’s clinical trials website, www.clinicaltrials.gov.

*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date. 

Updated 06/30/22