What is Herceptin? 

It is not chemotherapy or  a hormone therapy.  It  is called a monoclonal antibody which utilises  the natural immune system to kill tumour cells. Although cancers grow mainly beyond normal growth control, they are sufficiently similar to the own body’s cells to enable them to hide from the immune system (the body’s defence mechanism against “foreign” attack).

There are, however, some subtle differences between cancer cells and normal cells. Some  of these differences may be detected  with special sensitive laboratory tests. In the case of  breast cancer there may be too many copies of a cancer-causing gene called an oncogene. This oncogene called  HER2 is part of a family of genes called c-erbB-2 (otherwise known as her-2/neu). Each HER2 gene results  in the expression of a receptor on the surface of the cell. If the gene makes too much receptor, it  is referred to as being “over expressed".  Cells that over express too much  of the HER2 gene can  be a specific target for therapies such as Herceptin. Technology now exists to make antibodies  in the laboratory called monoclonal antibodies. Specific antibodies  have been made to detect  and attach to  the HER2 receptors. The antibody is therefore known as anti-HER2 called trastuzumab or its commercial name Herceptin. 

How does Herceptin work? 

Herceptin works in a different way than standard cancer therapy, such as chemotherapy or hormone therapies. Herceptin® (Trastuzumab) is believed to function in three main ways: 

• Blocking tumour cell growth:  Herceptin binds to the HER2 (receptors) on the tumour cell surface and this stops the receptor signalling the  cell to grow and divide. 
• Signalling of the immune system:   Certain immune system cells, called natural killer (NK) cells, attach to Herceptin when it is bound to the tumour cells. The NK cells then detect an abnormality, and kill the tumour cell. 
• Working with chemotherapy:   Herceptin and chemotherapy work in different ways, but when given together, the two drugs can form a partnership (synergy) so kill tumour cells more effectively than either Herceptin or chemotherapy when given alone. 

Who is eligible for Herceptin? 

Patients must have tumours which over express the HER2 protein (see above). Herceptin  is currently approved for use in  patients whose cancer has spread from the breast to other sites (metastasised). It is usually given in combination with chemotherapy drugs called taxanes. It is sometimes given with other chemotherapy drugs at the discretion  of the oncologist but these combinations have not yet gained regulatory approval.  Herceptin can also be given on its own (monotherapy) if patients have received  a taxane or anthracycline containing chemotherapy regimens previously (or cannot tolerate these drugs).  For these indications the aim  of treatment is not to cure, but to control specific symptoms caused by the cancer.  This is otherwise known as palliative treatment. It is hoped that treatment improves the quality  of life; therefore the side effects from the treatment should not outweigh the benefits of shrinking the tumour. 

There is now emerging evidence that Herceptin is likely  to have a benefit after the initial diagnosis of HER2+ve breast cancer (adjuvant). These trials are very new and regulatory bodies have not yet given their approval. 

Preparation for Herceptin ? 

As Herceptin  is a very specific treatment, your doctor needs  to find out if your tumour over-expressesHER2 receptors before even considering treatment. This  is usually achieved by performing a special laboratory test on a small piece of you original tumour (from the time of your original surgery or biopsy). Occasionally, your doctor may need a more recent tumour for analysis  and may recommend a further biopsy. In either case the tumour is usually send  to a lab which specialises  in specific tests called immunohistochemistry. A report will be issued by the pathologist on whether your tumour over expresses HER2  and how much is expressed. Research has shown that 20-25%  of women have tumours which do over express HER2. If  the cancer does over express  HER2 it will look brown/red down the microscope (see 1st left picture). Pathologists have a scale of 0-3 depending on the intensity of staining, if it 1 or 0 it is regarded as HER-2 negative  and Herceptin should not be used as treatment If it is grade 2 then a more sensitive test called FISH is performed, which looks at  the DNA of the tumour cells (second left picture). All tumours which are FISH positive or have 3+ intensity staining on immunohistochemistry are eligible for Herceptin.   

How is Herceptin administered? 

Herceptin cannot be taken orally as it would be destroyed by your stomach. It is, therefore, given as a drip into a vein usually over 90 minutes followed by a period  of observation. Occasionally, it is possible to get an allergic reaction, particularly to  the first treatment. The nurses will therefore be checking "how you are feeling" and measuring your breathing, pulse and blood pressure blood regularly. If all goes well the drip can last 1-2 hours, but sometimes,  in response  to mild reaction, it may have  to be slowed down over several hours. Rarely if  the allergic reaction is prominent it has  to be stopped altogether and abandoned. To avoid a mild reaction often paracetamol and an antihistamine are given before the infusion. The dose is calculated by the weight of the patient,  this is most often 4mg/kg on the first day then 2mg/kg once a week. This treatment continues until  the tumour stops responding. However, based  on recent information your doctor may choose to give Herceptin every three weeks particularly if this coincides with  the chemotherapy visits. Herceptin is usually given within a cancer department or hospital. In some areas  of the country, after the first few treatments it may be possible to receive the Herceptin infusion in your own home provided these facilities have been set up and are available locally. As mentioned above, Herceptin may  also be given in conjunction with chemotherapy. The dose, frequency of treatment and side effects will also depend on  the chemotherapy drugs used. The rationale and the specific regimen will be explained to you by the doctors and nurses before therapy starts. 

Are there any side effects to Herceptin? 

When given with chemotherapy most  of the side effects relate to the chemotherapy drugs  (see chemotherapy). Herceptin generally does not make these worse.  Herceptin does have some mild side effects on its own which may occur  in addition to those caused by chemotherapy. As mentioned above this does  not mean you will definitely get them. It is also possible you may experience a side effect not mentioned here:- 

The early effects often are related to an "allergic" reaction. If they do occur, it is often while the drug is being infused or shortly afterwards. 

Potential side effects include: 

• Fever and sweating 
• Runny nose 
• Chills  
• Skin flushing - redness 
• Tightness in the chest or difficulty breathing 
• Discomfort in the throat 
• Agitation  

If associated with a fast pulse and lower blood pressure these symptoms indicate an early allergic reaction. As mentioned above if these symptoms are prominent the infusion has  to be slowed down or abandoned altogether. To avoid a mild reaction often paracetamol  and an antihistamine are given before the infusion. 

The ongoing effects  may occur at any time whilst you are receiving Herceptin. These are usually worse a day or two after the infusion and could include:- 

• Weakness, lethargy or tiredness 
• Headache
• Sore eyes 
• Joint pains 
• Nausea   
• Diarrhoea
• Skin rashes 
• Shortness of breath on exertion

Late side effects may occur after receiving Herceptin for some time. The most important  of these is heart damage - this is rare (In clinical trials around 4%). To ensure  patients receiving Herceptin do not  experience any damage to  the heart, all patients must have a test  for heart function before starting treatment  and at regular intervals (usually every few months) after starting Herceptin. These tests include an echocardiogram or MUGA scan. The risks  of the development  of heart damage are higher if you have previously received chemotherapy containing drugs called anthracyclines or if you already have an underlying heart or lung problem. 

How will I know  the treatment is working? 

Your doctor would require evidence that  treatment is helping particularly after a 2-3 months. This can be achieved from  a number  of sources including; an improvement  in a specific symptom such as pain, a shrinkage  of a lump on examination, improvements in a blood test  or often evidence from repeat X-rays  and scans such as CT  or MRI. If there is no palliative benefit by this time treatment may be stopped.