Who Should Get Targeted Therapy? Breast Cancer Guidelines 2020

Who Should Get Targeted Therapy? Breast Cancer Guidelines 2020

Targeted therapy are medications that target a specific molecule on breast cancer cells.

Targeted therapy may be used in people with invasive or metastatic breast cancer. Targeted therapy is usually given in combination with chemotherapy or with hormonal therapy. 

This blog post focuses on targeted therapy and which people should receive it.

What is Targeted Therapy?

Targeted therapy is medication that targets specific parts of cancer cells while causing less harm to normal cells. Targeted therapy is different from chemotherapy because chemotherapy affects only rapidly dividing cells. Targeted therapy is more specific because it is able to tell the difference between cancer cells and normal cells. It targets molecules that are seen more on cancer cells, which may cause less side effects from treatment. 

For people with newly diagnosed invasive breast cancer or breast cancer that has recurred, a sample of your breast cancer tissue that has already been removed will be taken to a laboratory to be studied. One thing they will study are the targets and receptors your breast cancer has, such as hormone receptors or HER2 receptors. The results of this study will be given to in your pathology report. The pathology report has information that is specific to your own breast cancer.

What Are The Targets in Breast Cancer?

As described above, targeted therapy targets, or aims at, specific molecules. These targets are tiny molecules are associated with cancer cells and sometimes help in the spread or growth of the cancer cells. These molecules may be proteins, hormones, or other small molecules that are in the cancer cells or attached to the cancer cells.

HER2 is a receptor made of protein. Every person with invasive breast cancer will be tested to see if their cancer has the HER2 protein or, in some people, the gene that codes for the protein. HER2 is involved in normal cell growth. Normal cells have a normal amount of HER2 protein. Breast cancer cells may have a larger-than-normal amount of HER2 protein. If breast cancer cells have a larger-than-normal amount of HER2, then drugs that “target” HER2 will likely be used.

Other molecules in breast cancer cells that led to the creation of targeted therapy are:

  • CDK4 and CDK6
  • BRCA1 and BRCA2
  • PIK3CA
  • PD-L1
  • NTRK fusion

Who Might Get HER2 Targeted Therapy?

People with invasive breast cancer, metastatic breast cancer, or recurrent breast cancer will be tested for HER2 receptors. If the breast cancer has a larger than normal amount of HER2 receptors, then the breast cancer is called “HER2-positive” or HER2(+).

Above is a simplified example of two cells. The cells are the pink circular image on the picture. The purple items are HER2 proteins. 

The cell on the left is a normal breast cell. Notice how it only has two HER2 proteins on the cell. 

The cell on the right is a breast cancer cell. This cell has larger-than-normal amounts of HER2 on it. This cell has over 15 HER2 molecules. 

This is a simplified example of how cancer cells may have larger-than-normal amounts of specific receptors, while normal cells will have a normal amount. The numbers discussed above are only examples and not exact numbers that a real cell may have. 

People with HER2-positive breast cancer may get targeted therapy. The targeted therapy are drugs that treat cancer by targeting HER2 on cancer cells. A few of the medications that target HER2 are:

  • Pertuzumab (brand name Perjeta)
  • Trastuzumab (brand name Herceptin)
  • Pertuzumab, trastuzumab, hyaluronidase-zzxf combination (brand name Phesgo)
  • Tucatinib (brand name Tukysa)
  • Ado-trastuzumab emtansine or T-DM1 (brand name Kadcyla)
  • Fam-trastuzumab deruxtecan-nxki (brand name Enhertu)
  • Lapatinib (brand name Tykerb)
  • Neratinib (brand name Nerlynx)

For HER2-positive breast cancer, targeted drugs are usually used in combination with other medication. Your doctor will use many factors to make a specific treatment plan for you. You will be given a combination of medications to treat your cancer specifically.

These are several scenarios in which you might receive HER2 targeted therapy:

Stage IV recurrent or metastatic breast cancer that is HER2 receptor-positive and hormone receptor-positive 

They will receive HER2 targeted therapy in combination with one kind of hormonal therapy:

HER2 targeted therapy with →An aromatase inhibitor
(anastrozole, letrozole, or exemestane)
HER2 targeted therapy with →Fulvestrant
HER2 targeted therapy with →Tamoxifen

People that still have functioning ovaries (premenopausal) will receive treatment to induce menopause before receiving treatment.

Stage IV recurrent or metastatic breast cancer that is HER2-positive and hormone receptor-negative

They will receive HER2 targeted therapy in combination with chemotherapy

HER2 targeted therapy with →Chemotherapy 

Invasive breast cancer that is HER2-positive 

HER2 targeted therapy
(usually trastuzumab + / – pertuzumab) with →
Chemotherapy

Preoperative or post-surgery (adjuvant) therapy for breast cancer that is HER2-positive

Preoperative therapy is medication given before surgery. Adjuvant therapy is medication given after primary treatment to lower the risk of cancer returning. Also, this is for people with regional or local breast cancer that can be treated with surgery. 

HER2 targeted therapy
(usually trastuzumab + / – pertuzumab) with →
Chemotherapy

Who Might Get CDK4 and CDK6 Targeted Therapy?

People with metastatic breast cancer or recurrent breast cancer will be tested for additional targets. Patients with newly diagnosed breast cancer may be tested for additional targets as well.

CDK4 and CDK6 are proteins that help breast cancer cells divide. Medications that block CDK4/6 proteins are a form of targeted therapy. There are three medications that block CDK4/6 proteins: 

  • Abemaciclib (brand name Verzenio)
  • Palbociclib (brand name Ibrance)
  • Ribociclib (brand name Kisqali)

People in these scenarios with breast cancer may receive CDK4/6 blockers as targeted therapy:

Stage IV recurrent or metastatic breast cancer that is HER2-negative and hormone receptor-positive

They may receive CDK4/6 blockers in combination with one kind of hormonal therapy:

CDK4/6 blockers with →An aromatase inhibitor
(anastrozole, letrozole, or exemestane)
CDK4/6 blockers with →Fulvestrant
CDK4/6 blockers with →Tamoxifen

People that still have functioning ovaries (premenopausal) will receive treatment to induce menopause before receiving treatment.

Who Might Get Other Targeted Therapy

People With Breast Cancer TypeTargetTargeted Therapy Medications
Metastatic breast cancer with a BRCA1 or BRCA2 mutationPARPOlaparib (brand name Lynparza)

or

Talazoparib (brand name Talzenna)
HR(+) and HER2(-) subtypes with the PIK3CA mutations in stage IV recurrent or metastatic breast cancerPIK3CA mutationAlpelisib (brand name Piqray) 

*in combination with fulvestrant
HR(-) and HER2(-) breast cancer that expresses PD-L1 in stage IV recurrent or metastatic breast cancer
*HR(-) and HER2(-) breast cancer is also called triple negative breast cancer
PD-L1 expressionAtezolizumab (brand name Tecentriq) 

*in combination with albumin-bound paclitaxel
Metastatic breast cancer with a NTRK gene fusionNTRK fusionLarotrectinib (brand name Vitrakvi)

or

Entrectinib (brand name Rozlytrek)
Any breast cancer type with MSI-H or dMMR
*these are unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
PD-L1 expressionPembrolizumab (brand name Keytruda)
HR(+) and HER2(-) stage IV recurrent or metastatic breast cancermTOREverolimus (brand name Afinitor)

*taken with hormonal therapy (exemestane, fulvestrant, or tamoxifen)

References:

  1. National Cancer Institute Dictionary of Cancer Terms. cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms. Published February 2, 2011. Accessed December 10, 2020.
  2. National Cancer Institute. Targeted Cancer Therapies. cancer.gov. https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet. Updated July 17, 2020. Accessed December 10, 2020.
  3. Gradishar WJ, Anderson BO, Abraham J, et al. National Comprehensive Cancer Network Guidelines Breast Cancer. Version 5.2020 From the National Comprehensive Cancer Network; July 2020. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed  December 10, 2020.