About Breast Cancer > Treatment > Targeted Therapy
Targeted Therapy for Breast Cancer
What is targeted therapy?
Targeted therapy is the use of a drug that specifically attacks the abnormal growth pathway of cancer cells. Normal cells have normal growth pathways and so are not affected.
Each type of targeted therapy attacks different abnormal growth pathways that exist in different types of cancer, thereby interfering the ability of cancer cells to grow, divide, metastate and communicate with other cells.
Major types of targeted drugs:
|Monoclonal antibody drugs
||Targeted to inhibit the HER2 protein on the surface of cancer cells, blocking the signals directing the cells to grow.
|Tyrosine kinase inhibitor
||Targeted to inhibit Tyrosine kinase, an enzyme that activates malignant cellular activities
How are monoclonal antibody drugs used as targeted therapy?
Antibodies are part of the immune system. Normally, the body creates antibodies in response to an antigen (such as a protein in a germ) entering the body. The antibodies attach to the antigen in order to mark the antigen for destruction by the body's immune system.
In the laboratory, scientists have identified specific antigens in breast cancers and produce monoclonal antibodies as therapeutic drug to provide specific anti-tumour action within the body. A monoclonal antibody will attach to a matching antigen like a key fitting a lock. This technology allows treatments to target specific cells.
What is HER2 over-expression?
The HER2 ( human epidermal growth factor receptor 2) gene, in normal breast cell, is responsible for making the HER2 protein that transmits signals directing cell growth from the outside of the cell to the nucleus inside the cell.
In HER2 over-expressed (HER2-postive) breast cancer, there is an increase in the number of copies of the HER2 gene. This results in an increased amount of the HER2 growth factor receptor protein on the tumor cell surface. The over- production of HER2 protein amplifies the growth signal causing the cells to divide, multiply and grow more rapidly. Research has shown that HER2 positive breast cancer is more aggressive than other types of breast cancer.
Why is HER2 testing important?
About 20% of women with invasive breast cancer are HER2 over-expressed (HER2-positive). The monoclonal antibody treatment is applicable only to patients whose breast cancer is identified as HER2 over-expressed (or HER2 positive) in standard testing. Hence, it is very important to find out the cancer’s HER2 status.
How to test HER2?
Tests for HER2 are:
- FISH test (Fluorescence In Situ Hybridisation)
- CISH test (Chromogenic In Situ Hybridisation)
- IHC test (ImmunoHistoChemistry)
Is HER2 over-expression inherited?
HER2 over- expression is not inherited from parents while breast cancer genes such as BRCA1 and BRCA2 are inherited.
Anti-HER2 over-expression treatment - Trastuzumab (Herceptin)
What is Trastuzumab (Herceptin)?
The discovery of HER2 gene amplification in breast cancer patients led to the development of Trastuzumab (Herceptin), an artificial monoclonal antibody which acts against the HER2 protein on the surface of breast cancer cells. Trastuzumab (Herceptin) was approved by the FDA in 1998 to be used in first line treatment in HER2 over-expressed breast cancer patients, and was approved in 2006 for the adjuvant treatment of patients with HER2 over-expressed breast cancer.
How does it work?
- can be effective in early stage and metastatic HER2 over-expressed breast cancer.
- according to pivotal studies, Trastuzumab(Herceptin) identifies the HER2 breast cancer cells and works by
Interfering the growth of cancer cells
Attracting the body’s own immune cells to help destroy the cancer cells
- can work alone or in combination with chemotherapy to destroy HER2 over-expressed cancer cells.
- according to clinical studies, patients who progress on prior Trastuzumab (Herceptin) treatment would benefit from continuation of Trastuzumab (Herceptin) plus chemotherapy. In addition, publications show that Trastuzumab (Herceptin) could prolong overall survival in patients with brain metastases.
How is Trastuzumab (Herceptin) used?
- Trastuzumab (Herceptin) is given by slow intravenous infusion.
- It can be given once a week or once every three weeks. It works alone or together with chemotherapy. Prescription is decided by the doctor.
- The dosage depends on the patient’s body weight. The first- time infusion of Trastuzumab (Herceptin) is usually a higher dose (a loading dose).
- Current recommendation on the duration for using Trastuzumab (Herceptin) in early-stage breast cancer is one year.
What are the side effects of Trastuzumab(Herceptin)?
Very common side effects include:(>10 % patients experience the side effects)
Side effects include#: (1-10% patients experience the side effects)
- Infusional reactions include fever, nausea, vomiting, headache, diarrhoea, joint pain, muscle pain and rash. These allergic reactions usually occur after first infusion.
- Influenza-like illness, back pain, weight loss, loss of appetite, dry skin, leucopenia, bone pain.
- Cardiac problems including those without symptoms (reduce heart function) and those with symptoms (congestive heart failure). Trastuzumab and Anthracycline chemotherapy (Epirubicin or Doxorubicin) cannot be given together because both of them are toxic to the heart. People who have received both treatments are at a higher risk of developing heart problem.
- Trastuzumab (Herceptin) should be withdrawn in any event of a decline in heart function.
- Before and in the process of Trastuzumab treatment, your doctor should check your heart performance and conduct an echocardiogram.
- Rare side effects include severe allergic reactions, lung problems, and infusion reactions.
- Side effects vary with persons. You can consult your doctor for any questions or concern about side effects.
- If you experience swelling, chest pain, or severe shortness of breath, inform your doctor immediately.
Do all HER2 positive patients need Trastuzumab (Herceptin)?
Not all HER2 positive breast cancer patients need Trastuzumab (Herceptin). The HER2 positive patients with recurrent or metastatic disease require anti-HER2 treatment (e.g. Herceptin alone or in combination with hormonal therapy or chemotherapy).
In adjuvant treatment of early stage HER2 positive breast cancer, anti-HER2 therapy is indicated in intermediate and high risk patients (patients with lymph node involved or tumour larger than 1 cm). Currently, Herceptin is used together with chemotherapy either in sequence or in combination. There may be different preference by individual doctors. Duration of Herceptin treatment is one year.
Tyrosine kinase inhibitor - Lapatinib (Tykerb)
What is Lapatinib (Tykerb)?
Lapatinib (Tykerb) is a targeted breast cancer therapy with proven therapeutic effects, mainly in HER2 over-expressed breast cancers. The drug, together with the oral chemotherapeutic agent Capecitabine (Xeloda) was approved by the FDA in 2007.
It is used on refractory HER2 over-expressed breast cancer patients who are previously exposed to chemotherapy and Trastuzumab. It is an orally administrated drug widely recognised by patients, and is found to be effective in disease refractory to Trastuzumab.
How does it work?
- together with Capecitabine, is used on women with HER2 over-expressed, advanced or metastatic breast cancers.
- is a small molecule tyrosin kinase inhibitor which passes through the cell membrance to block the HER2 receptors inside the cell. This stops growth signals from being sent to cancer cells
- works inside the cell (while Trastuzumab works outside the cell).
- is more able to penetrate the blood brain barrier due to its small size. It reaches tumours deeper in the central nervous system than Trastuzumab does. This is important because up to one third of metastatic HER2 over-expressed breast cancers ultimately develop brain metastases.
How is Lapatinib (Tykerb) used?
- Lapatinib(Tykerb) is a tablet that is taken orally with Capecitabine.
- It is taken daily before or after meal.
- You should consult your doctor for the dosage and frequency of taking Lapatinib.
What are the side effects of Lapatinib in combination with Capecitabine ?:
Very common side effects include*: (>10% patients experience the side effects)
Loss of appetite, diarrhea, nausea, vomiting, rash, fatigue, poor digestion, dry skin, mucosal inflammation, constipation, abdominal pain, hand-foot syndrome, muscosal inflammation, back pain and insomnia.
Common side effects:(1-10% patients experience the side effects)
Other uncommon side effects: (0.1-1% of patients experience the side effects)
- Left ventricular ejection fraction (LVEF) have been reported in approximately 1% of patients.
- LVEF should be evaluated in all patients prior to initiation and continue to be evaluated during treatment to ensure LVEF does not decline to an unacceptable level.
- Paronychia and headache
Interstitial lung disease, inflammation of lung tissues and liver damage.
Not everyone taking Lapatini (Tykerb) has side effects. You can ask your doctor for further information
Special thanks to Dr. Kwan Wing Hong for editing
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