Targeted therapy, a form of precision medicine, is a type of treatment that stops or slows breast cancer by interfering with specific areas of cancer cells that are involved in the cancer cell’s growth processes. Targeted therapies are a type of systemic treatments (those that go throughout the body), but they differ from other systemic treatments, like chemotherapy.
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 an effort 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, and 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.
There are several types of targeted therapy that are used in treating advanced breast cancer, including:
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:
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
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 inhibitor available to treat certain forms of metastatic 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
PIK3CA is the most commonly mutated gene in HR+/HER2- breast cancer; approximately 40% of patients living with HR+/HER2- breast cancer have this mutation. Piqray is the first PI3K inhibitor approved for advanced or metastatic breast cancer that is hormone receptor-positive and HER2 negative and has a mutation in the PIK3CA gene.2
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 targeted therapies can include:
Skin or nail problems, including rashes or discoloration of nails
Reductions in the number of red blood cells, white blood cells, and/or platelets
Targeted therapy: monoclonal antibodies, anti-angiogenesis, and other cancer therapies. Chemocare. Available at http://chemocare.com/chemotherapy/what-is-chemotherapy/targeted-therapy.aspx. Accessed 9/20/18.
Targeted cancer therapies. National Cancer Institute. Available at https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet. Accessed 9/20/18.
Incorvati JA, Shah S, Mu Y, Lu J. Targeted therapy for HER2 positive breast cancer. Journal of Hematology & Oncology. 2013;6:38. doi:10.1186/1756-8722-6-38.
Targeted therapy for breast cancer. American Cancer Society. Available at https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html. Accessed 9/20/18.
Lynparza product website. AstraZeneca. Available at https://www.lynparza.com/breast-cancer/what-is-lynparza.html. Accessed 8/22/18.
Clancy, S. (2008) DNA damage & repair: mechanisms for maintaining DNA integrity. Nature Education 1(1):103. Available at https://www.nature.com/scitable/topicpage/dna-damage-repair-mechanisms-for-maintaining-dna-344. Accessed 8/22/18.
Afinitor product website. Novartis Pharmaceuticals. Available at https://www.us.afinitor.com/metastatic-breast-cancer/. Accessed 8/31/18.