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 are drug therapies.

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

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

Learn about clinical trials for people with metastatic breast cancer and access a web-based clinical trial matching tool – the Metastatic Trial Search.

Learn what Komen is doing to help people with metastatic breast cancer

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors

CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors are a class of drugs designed to interrupt the growth of cancer cells.

Abemaciclib (Verzenio), palbociclib (Ibrance) and ribociclib (Kisqali) are CDK4/6 inhibitors FDA-approved for breast cancer treatment. They are used in combination with hormone therapy to treat hormone receptor-positive, HER2-negative metastatic breast cancers.

Other CDK4/6 inhibitors for metastatic breast cancer treatment are under study. The use of CDK4/6 inhibitors in the treatment of hormone receptor-positive, HER2-negative early breast cancers is also under study [73].

HER2-targeted antibody 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) [23-24]. The HER2 protein is important for cancer cell growth.

Trastuzumab (Herceptin), pertuzumab (Perjeta) and margetuximab (Margenza) are special antibody drugs designed to target HER2-positive cancer cells. These drugs are FDA-approved for the treatment of HER2-positive metastatic breast cancers.

Other HER2-targeted antibody drugs are under study.

HER2 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.

The antibody drug trastuzumab (Herceptin) is designed to target HER2-positive cancer cells.

The HER2 antibody-drug conjugates ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) and fam-trastuzumab deruxtecan (Enhertu) are FDA-approved for the treatment of HER2-positive metastatic breast cancer.

Other HER2 antibody-drug conjugates are under study.

Tyrosine kinase inhibitors

Tyrosine kinase inhibitors are a class of drugs that target enzymes important for cell functions (called tyrosine-kinase enzymes).

These drugs can block tyrosine-kinase enzymes at many points along the cancer growth pathway.

The tyrosine-kinase inhibitors tucatinib (Tukysa), lapatinib (Tykerb) and neratinib (Nerlynx) are FDA-approved for the treatment of HER2-positive metastatic breast cancer.

Other tyrosine kinase inhibitors 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, not the person). This mutation can affect PI3 kinase and cause the tumor to grow.

PI3 kinase inhibitors are a class of 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 drugs that treat metastatic breast cancers with a PIK3CA tumor gene mutation (such as the drug capivasertib) are under study [74].

PARP inhibitors

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of drugs 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 only used to treat metastatic breast cancer in people who have a BRCA1 or BRCA2 inherited gene mutation. BRCA1/2-related breast cancers seem to be sensitive to DNA damage involving the PARP enzyme.

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.

Recent findings suggest women with metastatic breast cancer who have a PALB2 inherited gene mutation may also benefit from treatment with olaparib [105].

Other PARP inhibitors, such as veliparib, are under study [75].

Immunotherapy

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

Immunotherapy drugs (including vaccines) for breast cancer haven’t shown results as strong as for other cancers. However, some immunotherapy drugs may be helpful in treating some 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.

Atezolizumab (Tecentriq)

Early data showed the checkpoint inhibitor immunotherapy drug atezolizumab benefited some women with metastatic breast cancer so this drug was given accelerated FDA approval in 2019 [51]. 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 have cells with higher levels of the protein Trop-2 than other breast cancers (they express Trop-2). 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.

Other Trop-2 antibody-drug conjugates are under study.

Histone deacetylase (HDAC) inhibitors

Histone deacetylase (HDAC) inhibitors are a class of drugs that target enzymes important for some cell functions (called HDAC enzymes).

These drugs 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 [76]. 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 cannot 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 [77].

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.

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 SERD fulvestrant (Faslodex) is FDA-approved to treat hormone receptor-positive metastatic breast cancer.

Other SERDs are under study [78].

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 [79-80].

The more circulating tumor cells in the blood, the more advanced the metastatic breast cancer is likely 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 [81-84].

Circulating tumor cell and circulating tumor DNA tests (sometimes called liquid biopsies) are not used to guide treatment. This is because they haven’t been shown to offer benefit [4,85-88].

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 about $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

 

BreastCancerTrials.org in collaboration with Susan G. Komen® offers a web-based clinical trial matching tool – the Metastatic Trial Search. This tool makes finding out about metastatic breast cancer clinical trial options easy and fast.

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 09/10/21