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In metastatic breast cancer, targeted drugs treat cancer by targeting specific molecules inside the body.
Your treatment plan will be designed based on many individual factors. One of these factors is the “biological targets” that your cancer has, which will help decide which targeted drugs are chosen. Targeted drugs will not be used in every person, but if it is used, it may be combined with hormonal drugs or chemotherapy.
Before we discuss targeted drugs for metastatic breast cancer, let’s walk through some background information.
What Is Metastatic Breast Cancer?
Metastatic cancer is cancer that has spread from the primary site (where it started) to another place in the body. In metastatic breast cancer, the cancer has broken away from the breast (where it first formed) and has traveled in the body to form new tumors in other areas of the body (such as the lungs, kidneys, or brain). Even though the metastatic breast cancer is now found in other parts of the body, the cancer itself is still breast cancer.
Metastatic breast cancer is also known as stage IV breast cancer. Although you may have been diagnosed with another stage of breast cancer initially, it is possible for breast cancer to progress to metastatic stage IV breast cancer.
What Are Targeted Drugs?
Targeted drugs are medications that treat cancer by targeting specific parts of the cancer cell. These targets are specific molecules (such as proteins or receptors) that the cancer cells have in larger-than-normal amounts. Normal, healthy cells could have these same molecules, but not in large amounts like cancer cells. When targeted drugs target these specific molecules, they stop the growth and spread of cancer cells.
Targeted Drugs Versus Chemotherapy
Chemotherapy targets cells that are rapidly dividing. Cancer cells divide more rapidly than most normal cells. Some normal and healthy cells–including those in your mouth and hair, also divide rapidly. This is what causes effects. Chemotherapy harms cancer cells more than it does most normal cells.
As explained above, targeted drugs target specific molecules on the cancer cells. This allows the medication to be select, or choose, those cancer cells more so than instead of normal or healthy cells. Targeted drugs usually block tumor growth. Although these drugs target cancer cells more specifically, they still can have side effects.
Targets In Metastatic Breast Cancer
Breast cancer can have different types of molecules, called “markers.” These markers are on or in the cancer cells.
Your doctor will have your tumor tested for these markers. The most common markers you may have heard of are hormone receptors will do lab tests to see what targets or biomarkers your breast cancer cells have. Biomarkers will be different for each person. They help your doctor learn more about your individual cancer. This will be just ONE of the tools that your doctor uses to guide your treatment plan for metastatic breast cancer.
This article will focus mainly on the HER2 protein biomarker for targeted drugs. A few other targeted drugs that target different biomarkers are discussed later.
HER2 Protein
HER2 is short for human epidermal growth factor receptor-2. HER2 is a protein that is involved when normal, healthy cells grow. However, it is also made in very large amounts in certain cancer types, like breast cancer. About one in five people with breast cancer has abnormal amounts of HER2 on the cancer cells. Your tumor will be tested to see if it has this HER2 protein made in larger-than-normal amounts.
When You May Receive Targeted Drugs
Most often, targeted drugs are used in combination with chemotherapy or hormonal drugs. The choice depends on multiple factors such as the biological make-up of your tumor (such as HER2 status), the location of the metastasized tumor (where the tumor traveled in your body), how long you have had the cancer, and what treatments you tried in the past. Many other factors will also be considered.
The biological make-up of your tumor can be studied with specific lab tests. One of the main targets that is looked for in metastatic breast cancer is the HER2 protein, as explained in sections above. If your cancer has the HER2 protein in a larger-than-normal amount, then your status will be HER2-positive, or HER2(+). If your cancer does not have the HER2 protein in a larger-than-normal amount, then your status will be HER2-negative, or HER2(-).
Targeted drugs that treat HER2(+) metastatic breast cancer are mostly combined with chemotherapy or hormonal drugs. The choice of which drug you will get depends on many factors. One of these factors is whether the breast cancer cells also have a larger-than-normal amount of hormone receptors (HR). HR(+) means that the cancer has large amounts of hormone receptors, and HR(-) means that the cancer does not have large amounts of hormone receptors.
HER2(+) and HR(+)
- The cancer has both HER2 proteins and hormone receptors. The combination will likely be targeted drugs plus hormonal drugs.
HER2(+) and HR(-)
- The cancer has HER2 proteins but does not have hormone receptors. The combination will likely be targeted drugs plus chemotherapy.
HER2 targeted drugs are one type of many targeted drugs in breast cancer treatment. There are other situations that may lead your doctor to choose targeted drugs. Remember, your doctor will be looking at you as an entire picture, not just the biological make-up of your cancer. Your biomarkers are just one piece to the puzzle that will influence the treatment plan that your doctor designs.
First we will discuss HER2 targeted drugs, then we will discuss other targeted drugs for metastatic breast cancer.
HER2 Targeted Drugs
The following medications are HER2-targeted drugs. These can be used in HER2(+) metastatic breast cancer. If the cancer is also HR(+), then hormonal drugs may be added to the HER2-targeted drugs. If the cancer is HR(-), then chemotherapy may be added to the HER2-targeted drugs.
Perjeta (generic name is pertuzumab)
This medication is given by an infusion into your vein over a period of time.
You may have a combination of symptoms called “infusion reactions” that look like allergies and may include redness, fever, or itching. You may be given medication to prevent this from happening.
A few side effects that Perjeta may cause are extreme tiredness, dizziness, or weakness. It may also cause a headache, nausea, vomiting, diarrhea, or a decrease in appetite.
Herceptin (generic name is trastuzumab)
This medication is given as an infusion into your vein over a period of time.
Herceptin may cause you to feel overall tired or weak. It may cause headache, chills, or pain in your bones, muscle, or joints. It may also cause tummy issues like nausea, vomiting, or diarrhea.
Phesgo (combination of pertuzumab, trastuzumab, hyaluronidase-zzxf)
This medication is a combination of Perjeta + Herceptin that can be given as an injection under the skin.
It can be substituted anywhere where the combination of Perjeta + Herceptin is given as an infusion. Since it is an injection, it is given in less time than an infusion of Perjeta + Herceptin.
Phesgo cause hair loss, skin rashes, or dry mouth. This can also cause diarrhea, constipation, loss of appetite, nausea, and vomiting.
Tukysa (generic name is tucatinib)
This medication is given as a tablet by mouth twice a day. It can be taken with or without food, but the tablet should be swallowed whole.
Tukysa should be stored in its original container and protected from moisture. The bottle has a small desiccant inside that is used to absorb any moisture. This should be kept inside, even after the packaging is opened. After opening the original container, the tablets are only good for three months. After three months, speak with your healthcare providers about safely throwing away the unused tablets.
A few side effects that have been reported are general loss of strength and energy, mouth sores, tummy issues, loss of appetite, headache, and joint pain.
Kadcyla (generic name is ado-trastuzumab emtansine or T-DM1)
This medication is a HER2-targeted therapy with a mini chemotherapy molecule (emtansine) attached to it.
Kadcyla is given as an infusion into the vein over a certain period of time.
This medication can cause general tiredness, headache, dry mouth, or mouth sores. It can also cause joint or muscle pain, nerve pain, or tummy issues like nausea, constipation, diarrhea, and vomiting.
Enhertu (generic name is fam-trastuzumab deruxtecan-nxki)
This medication is a HER2-targeted therapy that has a mini chemotherapy molecule (deruxtecan) attached to it.
Enhertu is given as an infusion into the vein over a period of time.
It may cause you to feel overall tiredness and weakness. You may get a headache, experience hair loss, or have tummy issues like nausea, vomiting, constipation, or diarrhea. It could also decrease your appetite, or cause nosebleeds or mouth sores.
Tykerb (generic name is lapatinib)
This is a tablet taken by mouth once a day, at the same time each day. This should be taken on an empty stomach 1 hour before a meal, or 1 hour after a meal. Tykerb should not be taken with grapefruit.
This medication may cause headaches, skin rashes, tiredness, mouth sores, and tummy issues like nausea, vomiting, diarrhea, or bloating.
Nerlynx (generic name is neratinib)
This is taken as a tablet by mouth once daily. Grapefruit should be avoided while using this medication.
The most common side effect of Nerlynx is diarrhea, so you may be given a medication with Nerlynx to prevent diarrhea. Other side effects are skin rashes, tiredness, mouth sores, tummy pain, nausea, or vomiting.
Other Targeted Drugs
There are targeted drugs that can be used if metastatic breast cancer does not have larger-than-normal amounts of the HER2 protein. This is called HER2-negative, or HER2(-), metastatic breast cancer. The choice of medication will depend on many factors. One of these factors is if hormone receptors are present. HR(+) means that the cancer has hormone receptors. HR(-) means that the cancer does not have hormone receptors.
HER2(-) and HR(+)
- A group of medications called CDK4/6 blockers is used. These are usually combined with hormonal drugs.
HER2(-) and HR(-)
- This is also called triple negative breast cancer.
- Trodelvy is the targeted drug that is used in triple negative breast cancer. Other medications used in triple negative breast cancer are different combinations of chemotherapy.
CDK4/6 Blockers
This is a protein that some breast cancer cells may have. The following are targeted drugs that target this protein.
Verzenio (generic name is abemaciclib)
This is a tablet taken by mouth twice a day, at the same time each day. The tablet should be swallowed whole, and not crushed or chewed. Grapefruit should be avoided when using this medication.
Common side effects are tummy issues such as diarrhea, nausea, decreased appetite, stomach ache, vomiting, and constipation. Other side effects are weight loss, hair loss, general weakness or tiredness, headache, and dizziness.
Ibrance (generic name is palbociclib)
This is a tablet or capsule taken by mouth once a day, at the same time each day. Ibrance should be swallowed whole, and not crushed or chewed. Grapefruit should not be consumed while on this medication.
The tablets can be taken with or without food. The capsules should be taken with food.
Common side effects are nausea, diarrhea, vomiting, and loss in appetite. It may also cause hair loss, skin rashes, or general tiredness or weakness.
Kisqali (generic name is ribociclib)
This is a tablet taken by mouth once a day, at the same time each day. It is best taken in the morning. The tablets should be swallowed whole, not crushed or chewed. It can be taken with or without food, however, grapefruit should be avoided when taking Kisqali.
Common side effects are tummy issues such as nausea, diarrhea, vomiting, constipation, stomach ache, and loss in appetite. It may also cause headache, general weakness, dizziness, hair loss, skin rashes, and itching.
Targeted Therapy for Triple Negative Breast Cancer
Trodelvy (generic name is sacituzumab govitecan-hziy)
This is an infusion given by vein. Common side effects are overall tiredness and weakness. Trodelvy can also cause tummy issues like stomach ache, constipation, loss in appetite, diarrhea, nausea, and vomiting. Other side effects are hair loss, dry skin, skin rashes, and itching.
Additional Targeted Drugs
The following medications are additional targeted drugs that target different biomarkers than the ones listed above. They are additional medications either taken by themselves or added to other drug combinations.
The table below lists the drug name, the biomarker targeted, the breast cancer type it’s used in, how the medication is taken, and a few common side effects.
These drugs are additional targeted drugs that may be used alone, or may be added to other medications as a combination. They are used in certain circumstances.
Monitoring
If you experience any symptoms or side effects, let your doctor know immediately. Some side effects, like stomach problems, can be treated with medication.
Your medical team will be monitoring your symptoms and breast cancer progression closely. They will do lab tests and blood work to monitor the medication, medication side effects, and the cancer itself.
Birth Defects
These medications will cause severe birth defects. If you have functioning ovaries and are able to get pregnant, you should make sure to avoid pregnancy. If you are a male receiving treatment, speak to your doctor about contraceptives.
References:
- 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 September 9, 2020.
- National Cancer Institute Dictionary of Cancer Terms. cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms. Published February 2, 2011. Accessed September 9, 2020.
- 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 September 9, 2020.
- American Society of Clinical Oncology. Breast Cancer: Types of Treatment. cancer.net. https://www.cancer.net/cancer-types/breast-cancer/types-treatment. Approved July 2020. Accessed September 9, 2020.
- American Society of Clinical Oncology. Breast Cancer: Types of Treatment. cancer.net. https://www.cancer.net/cancer-types/breast-cancer/types-treatment. Approved July 2020. Accessed September 9, 2020.
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