HER2 positive breast cancer
HER2 (human epidermal growth factor) is a protein that can affect the growth of some cancer cells. It is found on the surface of normal breast cells.
What is HER2 positive breast cancer?
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HER2 (human epidermal growth factor) is a protein that can affect the growth of some cancer cells. It is found on the surface of normal breast cells. Some breast cancer cells have a very high number of HER2 receptors. The extra HER2 receptors stimulate the cancer cells to divide and grow. When there are higher levels of the HER2 protein in a breast cancer, it is called HER2 positive breast cancer.
The higher the level of HER2, the more likely the cell is to grow and divide. Between 15 and 25 out of every 100 women with breast cancer (15–25%) have HER2 positive cancers. Fewer men with breast cancer are thought to have HER2 positive cancers.
HER2 positive breast cancers tend to grow more quickly than HER2 negative breast cancers. However, effective treatments called targeted (biological) therapies have been developed to treat HER2 positive breast cancer. The drug most commonly used is trastuzumab (Herceptin ®).
Everyone diagnosed with breast cancer will have a test to check the HER2 level of the breast cancer cells.
Testing is usually done after you have had a sample of breast tissue removed (a biopsy) when you are first diagnosed. But it may also be done after you’ve had surgery to remove the cancer. Knowing if the cancer is HER2 positive or negative helps your doctors decide which treatments will be best for you.
If you have a breast cancer that comes back after initial treatment, you may have the HER2 levels checked again. This can be checked by taking another biopsy. In a small number of cases (1 in 5 or fewer), the HER2 level may have changed. Your specialist will advise you whether this is appropriate in your situation.
There are two main ways of testing for HER2. These are immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH).
IHC measures the level of the HER2 protein in the sample of tissue taken from the cancer. The HER2 level is graded from 0 to 3+.
0–1+ means there is a normal amount of HER2, and the cancer is HER2 negative.
3+ means there is a higher than normal level of HER2, and the cancer is HER2 positive.
If the result is 2+, guidelines recommend you have a FISH test (see below). The results of this test will help identify the people with a level of 2+ who will benefit from treatment with trastuzumab.
FISH (fluorescence in-situ hybridisation)
FISH measures the amount of a gene called the HER2/neu gene. This gene is responsible for the overproduction of HER2 protein in each cell. About 1 in 4 people (25%) with a 2+ result will have a positive FISH result.
The result will be either:
FISH negative – there is a normal level of the gene and the cancer is HER2 negative.
FISH positive – there is a higher level of the gene and the cancer is HER2 positive.
Your breast cancer specialist or breast care nurse will discuss your results with you.
Treatment overview for HER2 positive breast cancer
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HER2 positive breast cancer is treated in a similar way to other breast cancers. Surgery to remove the cancer is usually the first treatment for breast cancer. You may also have other treatments to reduce the risk of the cancer coming back. These include chemotherapy, radiotherapy and hormonal therapy.
Drug treatments called targeted therapies have been developed specifically to treat HER2 positive breast cancer. These include a drug called trastuzumab (Herceptin®). If you have a HER2 positive breast cancer, you will be given trastuzumab as well as other treatments to help reduce the risk of the cancer coming back.
Your specialist looks at the following things to decide which treatments are best for you:
the stage of the cancer (its size and whether it has spread outside the breast)
the grade of the cancer (how fast growing the cells are)
whether the cancer cells are HER2 positive
whether the cancer cells have receptors for the hormone oestrogen (which means they will respond to hormonal therapy).
If you have HER2 positive breast cancer that has spread to other parts of the body (secondary breast cancer), your treatment will depend on what treatment you have had before and how long ago this was.
If you have surgery, the type of surgery you have will depend on the size and position of the cancer. You and your doctor will decide which operation is best for your individual situation. Some people have chemotherapy and trastuzumab before surgery (called neo-adjuvant treatment). This may shrink the size of a large tumour so that when you have your operation, you may only need part of the breast removed instead of all of it.
Wide local excision (breast-conserving surgery)
Wide local excision is the removal of the breast cancer, together with some surrounding tissue. This is known as breast-conserving surgery. It removes the least amount of breast tissue, but leaves a small scar and sometimes a small dent in the breast. After a wide local excision, you will usually have radiotherapy to the remaining breast tissue. For most women, the appearance of their breast is good after this type of surgery.
Removing the breast (mastectomy)
Breast surgeons will usually try to remove only part of the breast if possible. But they may recommend you have the whole breast removed if:
the lump is large in proportion to the rest of your breast
there are areas of cancer in different parts of the breast
there is widespread ductal carcinoma in situ (DCIS) in the breast
you have had radiotherapy to the chest before to treat another cancer, such as Hodgkin lymphoma.
Surgery to lymph nodes
Your surgeon may remove some or all of the lymph nodes in your armpit to check them for cancer cells. This is for two reasons:
It gets rid of any cancerous lymph nodes (you may need more treatment if only some nodes were removed).
It gives information about the stage of the cancer, which helps when making decisions about having other treatments.
There are different types of lymph node surgery. Your doctor will explain which type they think is most suitable for you.
Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. Chemotherapy can be given in combination with trastuzumab.
You may have chemotherapy after surgery to reduce the chances of breast cancer coming back. This is called adjuvant chemotherapy.
Some women have chemotherapy before surgery. This is called neo-adjuvant chemotherapy. Chemotherapy given before surgery will reduce the risk of the cancer coming back and it can also shrink the cancer. This may mean you don’t need such a big operation. For example, your doctors may suggest you have a wide local excision instead of a mastectomy.
There are different groups of chemotherapy drugs. HER2 positive breast cancer is often treated with chemotherapy drugs called anthracylines and taxanes as well as some others. You’ll usually have a combination of two or more chemotherapy drugs.
Anthracycline chemotherapy drugs aren’t usually given at the same time as trastuzumab because they can both affect the heart. Your doctor or specialist nurse can give you more information about this. You will have tests to check your heart before and during your treatment.
Drugs used to treat breast cancer include:
Anthracycline drugs: Doxorubicin and epirubicin (pharmorubicin ®).
Taxane drugs: Paclitaxel (Taxol ®) and docetaxel (Taxotere ®)
Other drugs: fluorouracil (5FU), cyclophosphamide, methotrexate and capecitabine.
Chemotherapy can cause side effects, including increased risk of infection, feeling sick (nausea) and tiredness. Tell your doctor or specialist nurse about any side effects you have as there is usually something that can help.
Trastuzumab (Herceptin ®)
Trastuzumab is a type of drug called a monoclonal antibody. Monoclonal antibodies are sometimes called targeted therapies because they work by ‘targeting’ specific proteins (receptors) on the surface of cells. Trastuzumab locks on to the HER2 protein. This blocks the receptor and stops the cells from dividing and growing.
It is usually given following surgery and chemotherapy for primary breast cancer to reduce the risk of the cancer coming back. Even if you have a very small cancer that has not spread to the lymph nodes, your doctor may recommend treatment with trastuzumab.
You may have trastuzumab in combination with a course of chemotherapy. If you're having a combination of drugs which includes an anthracycline, you will usually start trastzumab after the anthracycline has finished.
Trastuzumab may sometimes be given with chemotherapy before surgery and then continued after surgery.
Because it can affect the way the heart works, you will have tests to check your heart before, during and after treatment. Some people with a history of heart disease or uncontrolled high blood pressure may not be able to have trastuzumab.
You can have trastuzumab as a drip into a vein (intravenous infusion) or as an injection under the skin (subcutaneously). It is usually given once every three weeks. If you have early breast cancer, you will usually have trastuzumab for a year. If the cancer is advanced or has spread elsewhere in the body, you will have trastuzumab for as long as it is controlling the cancer. Side effects tend to be mild and include flu-like symptoms, diarrhoea and headaches. Tell your doctor or specialist nurse about any side effects you have.
Lapatinib (Tyverb ®)
Lapatinib is another targeted therapy used to treat HER2 positive breast cancer. It works by blocking signals in the cancer cells that make them grow and divide. Blocking the signals causes the cells to die.
Lapatinib is a tablet that’s taken once a day. It is given with the chemotherapy drug capecitabine (Xeloda ®). The side effects are usually mild and include diarrhoea, a rash and tiredness. Lapatinib is a newer treatment so may not be widely available. You may be given it as part of a clinical trial. You can ask your doctor or breast care nurse whether lapatinib is suitable for you.
Pertuzumab (Perjeta ®)
Pertuzumab is another targeted therapy that locks on to the HER2 protein. It locks on to a different part of the HER2 protein from trastuzumab. It is given with trastuzumab and the chemotherapy drug docetaxol (Taxotere ®).
Pertuzumab is given as a drip (infusion) every three weeks with trastuzumab and continued for as long as the cancer is under control. Docetaxol is normally given for six doses and then stopped. The side effects of pertuzumab are similar to trastuzumab.
You may be given these drugs if you have just been diagnosed with breast cancer that has spread (secondary breast cancer) or as part of a clinical trial. As pertuzumab is a newer drug, it is not widely available on the NHS. Your doctor or specialist nurse can tell you whether pertuzumab may be suitable for you.
Trastuzumab emtansine (Kadcyla ®)
Trastuzumab emtansine is a combination of two drugs, trastuzumab and a chemotherapy drug.
Trastuzumab emtansine locks on to the HER2 proteins on the cancer cell. This blocks the receptors and stops the cells from dividing and growing. It also releases the chemotherapy drug directly into the cancer cell so that it damages and destroys it from inside the cell.
Radiotherapy treats cancer by using high-energy rays to destroy the cancer cells. It is given after breast-conserving surgery and sometimes after a mastectomy to reduce the risk of the cancer coming back. It can also be used to relieve pain and other symptoms caused by a cancer that has spread to other parts of the body, such as the bones and the brain.
Many breast cancers have hormone receptors and need the hormone oestrogen to grow. These are known as oestrogen receptor positive (ER positive) breast cancers. Hormonal therapy blocks oestrogen from attaching to the cancer cells, or reduces the amount of oestrogen in the body. It’s often given after surgery to reduce the risk of the cancer coming back or to control the cancer if it has spread to other parts of the body (secondary breast cancer).
HER2 positive breast cancers tend to have less hormone receptors but some do respond to hormonal therapy. Hormonal drugs include tamoxifen, anastrozole (Arimidex ®), letrozole (Femara ®) or exemestane (Aromasin ®).
Research into treatments for HER2 positive breast cancer continues, looking at new treatments or combinations of treatments. You may be asked to take part in a trial. Your doctor or specialist nurse will talk to you about any trials so that you understand the trial and what it involves. You may decide not to take part. Or you may choose to withdraw from a trial at any stage. You will still receive the best standard treatment available.
This page has been compiled using information from a number of reliable sources, including the electronic Medicines Compendium (eMC; medicines.org.uk). If you’d like further information on the sources we use, please feel free to contact us.
This information was reviewed by a healthcare professional.
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