Summary
Genetic mutations and cancer
Our bodies are made up of trillions of cells. Almost every cell has a nucleus containing a complete set of our genetic material - our DNA.
Inside the nucleus are structures called chromosomes. Tightly packaged up inside chromosomes is our DNA. Genes are short sections of DNA. Genes tell the body how to grow, work, and react to its surroundings. Genes do this by giving instructions to make proteins. Proteins are the molecules that actually do the work in cells. Genes give the instructions and proteins are the building materials made from those instructions. About two per cent of our DNA carries the instructions to make all the proteins our body needs to function, while the remaining DNA helps control how our genes work.
Our cells have a lifespan – they get old and die off. Some cells last only a few hours or days, yet others last for months or years or even a lifetime. The cells in our bodies continuously divide to grow. Each time a cell divides, it copies its DNA and sometimes, small copying mistakes can occur, called mutations.
Most mutations are harmless, and some are repaired automatically by our cells. Normally, our immune system gets rid of these mutated or altered cells but as we age our DNA repair mechanisms weaken and our immune system becomes less good at this. This means that some abnormal cells survive and multiply.
When DNA is damaged, it can change the instructions. Some mutations allow a cell to make too many copies of itself while others stop it from dying and yet others stop repairs from being made.
Cancer forms when accumulated DNA damage disables the mechanisms that normally control cell growth, repair, and death, allowing cells to grow and spread uncontrollably.
These changes occur only in the affected group of cells, which is why cancer can often be cured when detected early and removed before it spreads.
Cancer that spreads - metastatic cancer
All cancers begin in a single organ or tissue but over time, cancer cells can break off and travel to other parts of the body. Many of these cancer cells will die, but some will settle in a new location and begin to form new cancers. When cancer spreads in this way, it is called metastasis. Cancer cells that travel do not change. Breast cancer cells that move to the liver remain breast cancer cells. Doctors will treat metastatic cancer based on the type of cancer cells, not the location of the metastatic tumour.
What is HER 2 positive cancer?
HER-2 stands for Human Epidermal Growth Factor Receptor-2. In healthy cells, the HER-2 gene helps manage normal cell growth. It does this by making a protein called HER-2 protein which sits on the surface of cells. These proteins are growth receptors that act as signalling stations on the surface of cells. They receive signals and transmit them to the nucleus at the centre of the cell, stimulating the cell to grow and multiply.
In HER-2-positive cancer there are too many copies of the HER-2 gene in the tumour cell. More HER-2 genes mean that more growth factor receptors are made. More HER-2 growth factor receptors mean cells keep dividing and growing and they become tumours.
Most cancer is caused by somatic mutations
HER-2 mutations are termed somatic. This means they occur during life. They are not inherited - you were not born with them, and you cannot pass them on to your children. Only abnormal tumour cells carry the cancer-causing DNA mutations.
Why get tested?
HER-2 gene variant testing will be performed when you have a cancer that could have too much HER-2, such as breast cancer. HER-2 testing is performed on a sample of your tumour to see if you have an HER-2 amplification and will benefit from a targeted therapy.
If you have a positive result you will be able to be treated with a drug that is designed to target cancer specifically caused by HER-2 amplification. If you do not have HER-2 amplification, you will be treated with a different type of drug.
Herceptin treatment
HER-2-positive tumours tend to grow more aggressively than other tumours and respond differently to treatment.
In the past, HER-2-positive breast cancers meant an increased risk of recurrence. However, the use of Herceptin (trastuzumab) a targeted treatment against HER-2-positive cancers, together with chemotherapy, has dramatically improved outcomes for HER-2-positive breasts cancer, stomach and oesophageal cancers.
Herceptin works by blocking the ability of the cancer cells to receive signals that tell the cells to grow. It also flags the cell for destruction by the body's immune system.
Herceptin may be used alone or with some chemotherapy agents. Currently, it is approved in Australia for the treatment of HER-2-positive early-stage breast cancer and HER-2-positive advanced breast cancer. In cancer which has spread it is used together with a monoclonal antibody, Pertuzumab, and chemotherapy. It has also been approved for use in advanced or metastatic cancers of the stomach or lower oesophagus if they are shown to be HER-2 positive.
Other targeted treatment
Other medications that target the HER-2 pathway are available and can be used at various points together with or secondary to Herceptin. These include pertuzumab, lapatinib and ado-trastuzumab emtansine.
Having the test
Sample
Most HER-2 testing involves taking a sample of tumour tissue using a fine needle aspiration, needle biopsy or surgical biopsy.
Any preparation?
None
Your results
Two types of tests
There are two main ways to test HER-2 status in cancer tissue. These are IHC and FISH. IHC measures the amount of HER-2 protein present. FISH looks at the number of copies of the HER2 gene. The HER-2 gene is also called the ERBB2 (Erb-B2 receptor kinase2) gene, and you might see this on your report. The way your results are shown on your report will depend on which type of test has been used.
IHC test
IHC stands for immunohistochemistry. A sample of your tissue is dissected and stained so that the cells can be seen under a microscope. In this way, a pathologist can see how much HER- 2 protein is present. HER-2 receptors are made from this protein. Your results will appear as a score.
FISH test
FISH stands for fluorescence in situ hybridisation. This test detects the actual HER-2 genes in your tissue sample. The number of copies of the gene is counted to see if there are more than there should be. Your results will be presented as either positive or negative.
What may be on your report
A positive test result means a genetic mutation has been identified in the genes tested. The mutations identified may be called pathogenic or disease-causing variants. Variant is another name for mutation. The variants of strong or potential clinical significance are highlighted, and the results will help your doctors select the most appropriate treatment for the mutations identified. Genetic testing reports are highly complex. They typically present the most important and relevant information first followed by supplementary information.
Questions to ask your doctor
The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.
You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.
Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:
More information
Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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