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.

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 personalized clinical trial matching tool – the Metastatic Trial Search.

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 are under study for use in metastatic breast cancer treatment.

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

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

Other HER2-targeted antibody drugs, such as margetuximab, are under study [69].

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-nxki (Enhertu) are FDA-approved for the treatment of HER2-positive metastatic breast cancer.

Other HER2 antibody-drug conjugates are under study for the treatment of metastatic breast cancers.

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.

Tyrosine-kinase inhibitors include neratinib (Nerlynx), which is FDA-approved for the treatment of HER2-positive early and metastatic breast cancer, and lapatinib (Tykerb) and tucatinib (Tukysa), which are FDA-approved for the treatment of HER2-positive metastatic breast cancer.

Other tyrosine kinase inhibitors are under study for use in metastatic breast cancer treatment.

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 [70].

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 in breast cancer treatment for people who have a BRCA1 or BRCA2 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 gene mutation.

Other PARP inhibitors are under study for use in metastatic breast cancer treatment. 

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 have been seen for other cancers. However, they may be effective 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 atezolizumab (Tecentriq) is FDA-approved for the treatment of metastatic triple negative breast cancer that express (have a lot of) programmed cell death protein 1 (PD-L1).

The checkpoint inhibitor pembrolizumab (Keytruda) is FDA-approved to treat metastatic breast cancers that have a high tumor mutational burden [101]. This means there’s a high number of gene mutations in the cancer cells. This is not common.

Pembrolizumab is under study for the treatment of metastatic triple negative breast cancer [71].

Other immunotherapy drugs are under study.

Pembrolizumab and triple negative breast cancer

The checkpoint inhibitor immunotherapy drug pembrolizumab is under study for the treatment of metastatic triple negative breast cancer [71].

Some triple negative cancer cells have a receptor that limits the action of the protein called programmed cell death protein 1 (PD-1). Pembrolizumab may help take the brakes off PD-1 to allow the body to kill more cancer cells [71].

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-hziy (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 the selective HDAC inhibitor tucidinostat, are under study for the treatment of metastatic breast cancer [72].

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 [73].

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 the 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 for treatment of metastatic breast cancer [74].

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 [75-76].

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 [77-79].

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 [80-83].

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.

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Komen Perspectives

Read our perspective on living with metastatic breast cancer.*

 

 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.

Going forward, our commitment to research will contribute significantly to our ability to achieve our Bold Goal of reducing the current number of breast cancer deaths in the U.S. by 50 percent.

To date, Komen has provided more than $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 Cancer Clinical Trial Information Helpline

If you or a loved one needs information or resources about clinical trials, call our Clinical Trial Information 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 personalized 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 exhausted their 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.

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

*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.