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Breast cancer cells are normal breast cells with alterations of the genes, also called mutations. Cancer is a product of gene mutations, and these mutations are responsible for causing the cells to grow uncontrollably. If left untreated, these mutated cancer cells can spread to the rest of the body through the lymphatic system or the blood vessels. Genes are the “codes” for proteins created in the cell. There are several different gene mutations that can transform a healthy cell into a cancerous cell, but this brochure will only focus on breast cancer receptors, specifically HER2, EGFR, and VEGF receptors.
Receptors are cell proteins that are found on the surface of cells and attach themselves to certain substances, like hormones or neurotransmitters. These substances act as a signal similar to radio waves, instructing the cell to perform one task or to stop another. A healthy cell contains various receptors. These receptors are necessary for a cell to function normally. When a cell produces too many of these proteins, it begins to act differently. If a breast cell has too many HER2 receptors (which helps normal cells grow), the cell will grow uncontrollably.
HER2 – which is part of EGFR family receptors – and VEGF are two receptors that are commonly linked to breast cancer. An overexpression of either of the HER2 proteins is indicative of a poor prognosis.
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HER2, or the human epidermal growth factor receptor 2, is a receptor that is normally involved in cell growth and differentiation. In approximately 20% of breast cancer cases, there is a genetic mutation in the HER2 gene. This results in the “overexpression” or “amplification” of the HER2 protein localized on the surface of the tumor cell. The overexpression causes the tumor cell to divide, multiply, and grow faster than normal. Women with HER2+ breast cancer have a more aggressive disease, greater chance of experiencing a recurrence of breast cancer and poorer prognosis than women with other forms of breast cancer.
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VEGF, or vascular endothelial growth factor, is a protein that signals cells to start growing and forming new blood vessels. A normal cell does not produce a large amount of VEGF protein, but some cancer cells over-express it, releasing the protein into the area surrounding them. This causes blood vessels to form near the group of cancerous cells (known as a tumor), which provide nutrients and help it grow. This process is called “angiogenesis” and it is characterized by multiple steps where normal cells from the normal blood vessels – called endothelial cells develop a well regulated blood vessel network that will be used by the tumor to grow and proliferate. If the tumor continues to feed off of these new blood vessels, it will keep growing and eventually spread to the rest of the body.
Several receptors are responsible for the cancer’s behavior. These receptors oversee crucial cell activities such as: proliferation, survival, apoptosis (programmed cell death), and angiogenesis.
The discovery of new receptors and cancer pathways provides the ability to block specific cancer cell functions. In the last decade, a large number of small molecules called TKIs (tyrosine kinase inhibitors) and monoclonal antibodies (MoAbs) have emerged for the therapy of cancer.
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Most of these new TKIs consist of tablets or pills which are taken orally and the side effects differ considerably to those from regular chemotherapy.
In contrast, most of the MoAbs are large molecules that are given intravenously and have a particular spectrum of toxicity. Your doctor will discuss with you the most common side effects of each of these new drugs.
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As researchers have discovered more about these genetic mutations occurring in cancer cells, they have been able to develop drugs that specifically target these changes. This is referred to as ‘targeted therapy.’ Some types of breast cancer cells contain certain proteins that cause the cancer to grow more aggressively. Targeted therapy specifically targets these cells, preventing the proteins from fueling cancer cell growth.
Targeted therapies may be less harmful to healthy cells and more effective than traditional chemotherapy. They often have different (and less severe) side effects. An example of targeted therapy would be a drug that binds itself to HER2 receptors. These drugs act as a “key” and lock the receptors, preventing them from sending signals to the cell. By targeting that specific protein, the medication will only affect cells with the mutation, leaving healthy cells unharmed.
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This diagram shows trastuzumab (Herceptin®) and its role in limiting the spread of HER2+ cancer cells. Other drugs that target the HER2 protein include pertuzumab (Perjeta®) and trastuzumab emtansin (Kadcyla®).
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Currently, new tests are available to obtain information about the molecular characteristics of a tumor. These tests can identify specific genomic changes in the DNA of cells that cause the malignant cells to grow and multiply. By identifying the genomic alterations in the DNA of your cancer cells, doctors can recommend new targeted therapies that attack the specific mutations causing your cancer’s growth. Genomic profiling may be performed on a biopsy or blood sample. Next generation sequencing and liquid biopsies are now available. Both tests provide great information about tumor molecular characteristics.
A clinical trial is a study in which patients participate in order to evaluate a new treatment to treat a specific disease. Each clinical trial is structured to answer specific scientific questions and to develop better ways to help treat cancer patients.
Patients who participate in a clinical trial are among the first to receive new treatments before they are available to the general public. When the new treatments prove to be effective, those involved in clinical trials have the first chance to benefit from them. Before patients decide to take part in a clinical trial, they should understand the possible risks as well as the benefits.
Patients receiving treatment in clinical trials can experience side effects and other health risks depending on the patient’s condition and the type of treatment. Because the treatments are new and still under research, the risks are not always known ahead of time. However, most of the clinical trials are very safe, highly supervised not only for the doctor but many other organizations like FDA or NCI. In addition, the treatment may not be effective and the cost of the clinical trial may not be covered by insurance. Most side effects (such as nausea and hair loss) are temporary and gradually go away when treatment is stopped.
Every clinical trial chooses patients with certain types and stages of cancer. Patients who fit the guidelines of a particular clinical trial are usually referred to that trial by their own doctor or by a doctor who knows their case. Some patients find out about clinical trials from other sources. Each patient should have an understanding of her role in a clinical trial and be willing to participate. Patients should ask their doctor what they can expect if they take part in a trial.
Doctors and nurses in the trial explain the nature of the treatment. Patients are given an informed consent form that gives information about the potential benefits and risks involved in the trial. Patients should read the form, consider it carefully and ask any questions they might have. If the patient agrees to participate, she signs the form.
Patients are free to leave a clinical trial at any time for any reason.
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