Targeted Therapy
Targeted therapy, a form of precision medicine, is a type of treatment that stops or slows breast cancer by interfering with specific parts of a cancer cell that are involved in the cancer cell’s growth processes or by focusing on specific features that are unique to cancer cells. Targeted therapies are a type of systemic treatment in that they are designed to go throughout the body where the cancer cells are located. Other systemic treatments, like chemotherapy, work more broadly against multiple cell types throughout the body.
How are targeted therapies different?
Chemotherapy focuses on any cell that grows quickly. Cancer cells divide and grow quickly, but so do many healthy cells, including cells in the digestive tract, hair, bone marrow, and blood. This can cause multiple side effects. In contrast, targeted therapies focus on other specific features of cancer cells. In this way, targeted therapy attempts to provide treatment for cancer that does less damage to normal cells and causes fewer side effects.1,2
Another difference between targeted therapy and chemotherapy is that targeted therapies are generally cytostatic, meaning they block the growth and division of cancer cells. In contrast, chemotherapy is typically cytotoxic, meaning it kills cancer cells.2 In some cases, targeted therapy and chemotherapy may be used in combination to treat breast cancer.2
There are various types of targeted therapy that are used for the treatment of certain early-stage, advanced, and/or metastatic breast cancers. These are identified by their specific targets as shown in the list below:
- HER2-targeting agents
- CDK4/6 inhibitors
- PARP inhibitors
- mTOR inhibitors
- PI3K inhibitors
- Antibody-drug conjugates
HER2 targeted therapy
Some breast cancer cells have an excess of the human epidermal growth factor receptor 2 (HER2), and these are classified as HER2-positive breast cancers (HER2+). Breast cancers that are HER2+ are known to typically be more aggressive. That is, they can quickly grow and spread (metastasize). At diagnosis (initial and at a recurrence), a biopsy is taken of the breast cancer tumor to test for HER2, as well as other characteristics.3,4
Several treatments target the HER2 receptor, including:
- Herceptin® (trastuzumab)
- Kadcyla® (ado-trastuzumab emtansine)
- Nerlynx® (neratinib)
- Perjeta® (pertuzumab)
- Ogivri™ (trastuzumab-dkst)
- Tykerb® (lapatinib)
- Herzuma© (trastuzumab-pkrb)
- Ontruzant® (trastuzumab-dttb)
- Trazimera™ (trastuzumab-qyyp)
- Kanjinti™ (trastuzumab-anns)
- Herceptin Hylecta™ (trastuzumab and hyaluronidase-oysk)
- Enhertu (fam-trastuzumab deruxtecan-nxki)
- Tukysa™ (tucatinib)
- Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf)
- Margenza™ (margetuximab-cmkb)
Cyclin-dependent kinase 4 and 6 (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, which may cause the cancer cells to grow uncontrollably. By blocking CDK4/6, these targeted therapies can help slow the growth and division of breast cancer cells.4
CDK4/6 inhibitors for breast cancer include:
Poly (ADP-ribose) polymerase (PARP) inhibitors
PARP enzymes are important for cellular functions like DNA repair. DNA is replicated any time a cell divides, and the rapid growth of cancer cells creates more opportunities for DNA damage to occur. Damage to the DNA of cells, including cancer cells, can lead to cell death. Normally, cells have multiple ways of repairing any damage that may occur to the DNA. By blocking the PARP repair functionality, PARP inhibitors can limit the cancer cell’s ability to repair the DNA and can lead to the death of cancer cells. Two such PARP inhibitors available to treat certain forms of advanced breast cancer are Lynparza® (olaparib) and Talzenna® (talazoparib).5,6
Mammalian target of rapamycin (mTOR) inhibitors
mTOR is a protein that is normally involved in a cell’s ability to divide. Up to 70% of breast cancers have mutations on the mTOR pathway, and this mutation can fuel cancer’s growth. mTOR inhibitors block this pathway and can slow the growth of breast cancers. One such mTOR inhibitor available to treat certain forms of advanced breast cancer is Afinitor® (everolimus).4,7
PI3K inhibitors
PIK3CA is one of the most commonly mutated genes in breast cancer; approximately 40% of patients living with breast cancer have this mutation. Piqray is the first PI3K inhibitor approved to treat certain forms of advanced or metastatic breast cancer that is hormone receptor-positive and HER2 negative and has a mutation in the PIK3CA gene.2
Antibody-drug conjugates (ADCs)
Antibody-drug conjugates (ADC) combine the targeting ability of monoclonal antibodies with a specially designed chemotherapy medication using a chemical linker. Generally, by combining the antibody and chemotherapy medication together, the antibody portion helps to find and attach to the specific type of breast cancer cells, and once attached, the chemotherapy portion is released to attack the cancer cell.
Trodelvy™ (sacituzumab govitecan-hziy) is the first ADC approved for certain forms of triple-negative breast cancer.8
As mentioned above, Kadcyla and Enhertu are ADCs that target the HER2 receptor. They can be used to treat certain forms of HER2+ breast cancer.
Side effects of targeted therapies
While one goal of targeted therapies was to produce treatments that had fewer side effects to healthy cells, targeted therapies can still cause significant side effects.2 Each specific treatment has its own list of potential side effects, but some common side effects of certain targeted therapies can include:
- Diarrhea
- Fatigue
- Skin or nail problems, including rashes or discoloration of nails
- Reductions in the number of red blood cells, white blood cells, and/or platelets
These are not all the possible side effects of of targeted therapies. People should talk to their doctor about what are the potential side effects that can be expected with their specific treatment.
