Emerging Areas in Metastatic Breast Cancer Treatment

Antibody-drug conjugates

Antibody therapies are designed to target certain cancer cells. Antibody-drug conjugates are a combination of an antibody therapy and a chemotherapy drug.

The antibody-drug conjugates ado-trastuzumab emtansine (Kadcyla, T-DM1), trastuzumab deruxtecan (Enhertu) and sacituzumab govitecan (Trodelvy) are FDA-approved for the treatment of metastatic breast cancer.

Many different antibody-drug conjugates are under study for the treatment of metastatic breast cancer including drugs targeting HER2, HER3, Trop-2 and LIV-1. For example, the Trop-2 antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) is under study for the treatment of some metastatic breast cancers, including triple negative metastatic breast cancers [128].

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.

The SERDs fulvestrant (Faslodex) and elacestrant (Orserdu) are FDA-approved for the treatment of hormone receptor-positive metastatic breast cancers.

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

HER2-targeted therapies

The HER2 protein is important for cancer cell growth. Some breast cancers have high amounts of HER2 protein on the surface of the cancer cells (called HER2-positive breast cancers).

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.

HER3-targeted therapies

The HER3 protein is important for cancer cell growth. Some breast cancers have high amounts of HER3 protein on the surface of the cancer cells. HER3-targeted therapies are designed to treat these breast cancers.

HER3-targeted drugs for the treatment of metastatic breast cancer are under study.

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 cells, not the person.

A PIK3CA tumor gene mutation can affect PI3 kinase and cause the tumor to grow.

The PI3 kinase inhibitors alpelisib (Piqray) and inavolisib (Itovebi) are FDA-approved to treat some metastatic breast cancers that have a PIK3CA tumor gene mutation.

Other PI3 kinase inhibitors are under study for the treatment of metastatic breast cancers with a PIK3CA tumor gene mutation including some that cross the blood-brain barrier and some that target only specific types of PIK3CA mutations.

Other drugs that treat metastatic breast cancers with a PIK3CA tumor gene mutation are under study.

AKT inhibitors

The AKT (protein kinase B) enzyme is important in cell growth and division. Some breast cancers have a mutation in the AKT1, PIK3CA or PTEN gene. These gene mutations are in the genes of breast cancer cells, not the person.

These tumor gene mutations can affect AKT activity and cause the tumor to grow. AKT inhibitor drugs are designed to block AKT activity.

The AKT inhibitor drug capivasertib (Truqap) is FDA-approved to treat some metastatic breast cancers that have an AKT1, PIK3CA or PTEN tumor gene mutation.

Other AKT inhibitors for the treatment of metastatic breast cancer are under study.

Immunotherapy

Immunotherapy drugs help the body’s immune system attack cancer cells. Certain immunotherapy drugs may be helpful in treating some breast cancers.

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 some metastatic triple negative breast cancers. Pembrolizumab is under study for the treatment of other metastatic breast cancers.

Researchers are also studying how to identify the best biomarkers for immunotherapy and whether combinations of immunotherapy drugs can be effective for treatment.

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

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

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 hormone receptor-positive metastatic breast cancer.

PARP inhibitors

Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. Some chemotherapy drugs damage tumor DNA. PARP inhibitors work to stop PARP from repairing tumor DNA. This helps the chemotherapy kill the cancer cells.

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 or BRCA2 (BRCA1/2) inherited gene mutation.

Breast cancers in people who have a BRCA1/2 inherited gene mutation 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.

Study findings suggest women with metastatic breast cancer who have a PALB2 inherited gene mutation may also benefit from treatment with olaparib [91].

Newer PARP inhibitors that may be more effective and have fewer side effects than olaparib and talazoparib are under study.

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 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.

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 [92].

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

Bevacizumab is 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 and circulating tumor DNA tests are sometimes called liquid biopsies.

Circulating tumor cell levels can help predict survival for people with metastatic breast cancer [93-94]. 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. However, a large randomized clinical trial showed changing treatment based on circulating tumor cell levels did not result in longer survival [95]. So, circulating tumor cell tests are not used today to guide treatment and are not routinely performed outside of clinical trials [4,96-97].

Circulating tumor DNA is also under study for use in monitoring metastatic breast cancer and predicting treatment response [98-101]. However, it has not been proven to offer benefit in this setting and is not used today to guide treatment [96-97].

However, circulating tumor DNA testing can be used to check for specific tumor gene mutations (such as PIK3CA tumor gene mutations) with a blood test. This testing may be done instead of testing tumor tissue from a biopsy.

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

Clinical trials offer the chance to try new treatments and possibly benefit from them. After talking with your health care provider, we encourage you to consider joining a clinical trial for metastatic breast cancer.

Many clinical trials are available. Some are available as the first treatment for metastatic breast cancer. Others are for treatments later in the disease course. Consider joining a clinical trial when you’re newly diagnosed, when your oncologist is considering changing treatments or when there are limited treatment options.

Some clinical trials are done in one, or only a few, medical centers. Others are done in many places across the country. There may not be a clinical trial that’s right for you in your area. So, you may have to travel if you want to join.

If your medical center doesn’t offer clinical trials, your oncologist can refer you to a cancer center that does.

Susan G. Komen® Patient Care Center

If you or a loved one needs information or resources about clinical trials, the Patient Care Center can help. Contact the Komen Breast Care Helpline at 1-877-465-6636 or email clinicaltrialinfo@komen.org. The Patient Care Center navigators offer 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 for you 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. You can also register to receive Trial Alerts.

Learn more about clinical trials for people with metastatic breast cancer.

Learn what Komen is doing to help people find and participate in breast cancer clinical trials, including trials supported by Komen.

Expanded Access

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 EA Navigator tool has 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.

Updated 10/22/24