Emerging Therapies in Metastatic Breast Cancer

Researchers continue to look for new and better ways to treat advanced breast cancer. Treatments being evaluated in clinical trials can be generally grouped into the following categories:

• Targeted therapy, which interferes with specific areas of cancer cells that are involved in cancer cells' growth processes or focuses on specific features that are unique to cancer cells
• Immunotherapy, which uses the power of the body’s immune system
• Anti-angiogenesis, which blocks the blood supply to the cancer cells

Targeted therapy under investigation for advanced breast cancer

Targeted therapy is a type of treatment that stops or slows breast cancer. It does this by interfering with specific areas of cancer cells that are involved in the growth processes or by focusing on specific features that are unique to cancer cells. Targeted therapies focus on certain features of cancer cells in an effort to provide treatment for cancer that does less damage to normal cells and causes fewer side effects. This approach is also called precision medicine.^1,2

Targeted therapies being studied in the treatment of advanced breast cancer include:

• PI3K inhibitors
• Poly (ADP-ribose) polymerase (PARP) inhibitors
• Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors

PI3K inhibitors

PI3 kinase (PI3K) is a protein that plays a role in how cells grow and divide. About 40 percent of all advanced breast cancers that are estrogen-receptor positive (HR+) have a genetic mutation on the gene PIK3CA. This can cause an increase in the activity of PI3K and cause cancer to grow more quickly. PI3K inhibitors block PI3K and can slow or stop the growth of cancer. Alpelisib is the first PI3K inhibitor approved to treat certain forms of breast cancer.^3,4

PARP inhibitors

PARP enzymes are important for cellular functions like DNA repair. DNA is replicated any time a cell divides. The rapid growth of cancer cells creates more chances for DNA damage to occur. Damage to the DNA of cells, including cancer cells, can lead to cell death. Normally, cells have many ways of repairing DNA damage. By blocking the PARP repair function, PARP inhibitors can limit cancer cells' ability to repair the DNA. This can lead to the death of cancer cells. Some PARP inhibitors have been approved to treat certain forms of advanced or metastatic breast cancer. Others are still being researched.^3,5-7

CDK4/6 inhibitors

CDK4 and CDK6 are proteins that are important during a cell’s growth and replication cycles. In breast cancer cells, CDK4 and CDK6 may be overactive. This may cause the cancer cells to grow uncontrollably. By blocking CDK4/6, CDK4/6 inhibitors can help slow the growth and division of breast cancer cells. Some CDK4/6 inhibitors have been approved for use in the treatment of breast cancer. Others are under investigation.^3,8

Immunotherapy under investigation for advanced breast cancer

Normally, the body’s immune system fights disease and infection. The white blood cells recognize and destroy damaged or diseased cells and foreign invaders, like bacteria and viruses. Cancer cells can often mutate in a way to avoid detection by the immune system, and they grow out of control. Immunotherapies aim to help the immune system identify and destroy cancer cells. Several types of immunotherapy are being studied for the treatment of advanced breast cancer. This includes monoclonal antibodies and adoptive cell transfer.^9,10

Monoclonal antibodies are made in the lab to work like how antibodies produced by the body work. They can target specific areas of cancer cells and/or the pathway that allows cancer cells to avoid immune system detection. This includes blocking the function of specific proteins known as PD-L1 and PD-1. The PD-1 and PD-L1 proteins can help disguise cancer cells from the body’s T-cells (a type of white blood cell). This prevents T-cells from attacking the cancer cells, allowing cancer to continue to grow and survive. Certain monoclonal antibodies that target PD-L1 or PD-1 proteins disrupt this pathway. They may be available as an approved treatment option or through a clinical trial for certain forms of breast cancer.¹¹

Adoptive cell transfer is an emerging immunotherapy method that collects and uses a person's own immune cells to attack cancer. This process uses tumor-infiltrating lymphocytes (TILs). This is a type of white blood cell. Researchers first identify the specific mutations on the person’s cancer and identify which TILs can recognize them. These cells are removed from the person's body and grown in a lab to create a large number of them. This process can take several weeks. During this time, the person may be given treatments to reduce their immune cells. The TILs are then given back to the person, where they can generate an immune response to fight the cancer cells.^9,12

Anti-angiogenesis under investigation for advanced breast cancer

Angiogenesis is the development of new blood vessels. Tumors produce proteins that cause blood vessels to form. These blood vessels supply nutrients to cancer cells. They also provide an avenue for cancer to spread to other parts of the body through the bloodstream. Anti-angiogenesis drugs, or angiogenesis inhibitors, block certain proteins involved in the development of blood vessels or affect certain actions of the immune system. This can lead to anti-angiogenesis effects. Some angiogenesis inhibitors have been approved for use in other cancers. Others are being studied as a potential treatment for breast cancer.^3,13

Clinical trials

Certain people may be eligible to participate in clinical trials that are testing some of these new therapies. Clinical trials are an important part of the scientific process to find and prove the safety and effectiveness of new treatments. They also offer people a chance to receive the latest treatments and be closely monitored by doctors. Talk to your doctor about whether clinical trials are a good option for you.