Metastatic Breast Cancer
UNDERSTAND METATATIC BREAST CANCER
(26) Metastatic Breast Cancer
What is a monoclonal antibody?
Antibodies are a type of protein. The immune system produces them in response to foreign substances that may be a threat to the body, for example, chemicals, virus particles, bacterial toxins, or cancer. These foreign substances are called antigens. Each type of antibody is unique and defends the body against one specific type of antigen. Because an antibody binds only to a specific antigen, it can act as a homing device to a tumor cell.
The term monoclonal means from one specific type of cell. Monoclonal antibodies may be able to kill tumor cells themselves, or they may be linked with tumor killing substances. That “piggyback” system may allow treatment substances, such as drugs or radioactive materials, to be delivered directly to the tumor. Trastuzumab (Herceptin) therapy for HER2-positive breast cancer is one example of targeted therapy with monoclonal antibodies to treat metastatic breast cancer.
What is HER2-positive breast cancer, and how do I know if I have it?
Each normal breast cell contains the HER2 gene, which helps normal cells grow. The HER2 (also called HER2/neu or cERB-b2) gene is found in the DNA of a cell. This gene contains the information for making the HER2 protein receptor on the cell’s surface. In normal cells, the HER2 protein receptor helps send growth signals from outside the cell to the inside of the cell. These signals tell the cell to grow and divide. Some breast cancer cells have an abnormally high number of HER2 genes per cell. When this happens, too much HER2 protein appears on the surface of these cancer cells. This over expression of the HER2 protein causes cancer cells to grow and divide more quickly.
HER2-positive cancers are those that over express the HER2 protein receptor. Approximately 25 percent of breast cancer patients have HER2-positive tumors. It is very important for you and your doctor to know if your breast cancer is one of these. If it is, your treatment program will most likely contain trastuzumab (Herceptin), a monoclonal antibody that blocks the effects of the growth factor receptor protein HER2.
Your cancer’s HER2 status is determined by analyzing your breast cancer tissue in the laboratory. Pathologists will run tests either on the primary breast cancer tissue removed at the time of your breast surgery, or on material obtained from a biopsy of one of your metastases. There are two methods of testing for HER2 tumor status; immunehistochemistry (IHC) and fluorescence in situ hybridization (FISH). The scoring for an IHC test is from 0 to 31. Zero and 11 are HER2 negative; 21 is a borderline or equivocal result; and 31 is HER2 positive. FISH is a gene-based test used to determine the number of HER2 genes in the cells of the tumor.
Though it is not a perfect test, it is generally regarded as the definitive test for HER2 over expression. It is usually only done when the IHC result is borderline (21).
What is targeted therapy, and how does it work?
In recent years, scientists have made great strides in understanding the complicated biological pathways that cause cancer to develop, grow, and spread. Targeted therapies are perhaps the most exciting and promising application of this new knowledge. They use drugs that block specific biological pathways and proteins involved in the growth and spread of cancer. Because they are “smart drugs” that focus on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than traditional chemotherapy and less harmful to normal cells. This type of treatment is still quite new, and most targeted therapies are still in the research development phase. Some, however, have become available for general use over the past few years. Those used to treat metastatic breast cancer include bevacizumab (Avastin), trastuzumab (Herceptin), and lapatinib (Tykerb).
Not all targeted therapies are new. Drugs that target the hormone (estrogen and progesterone) receptors found on many breast cancer cells are among the oldest forms of breast cancer treatment. This type of breast cancer uses female hormones to fuel its growth. Drugs like tamoxifen block the estrogen receptor so that the cancer cells cannot get enough fuel and the cancer cells die. Other anti-estrogens, like the aromatase inhibitors anastrozole, decrease the amount of estrogen in postmenopausal women by blocking the aromatase enzyme needed to make estrogen.
Many of the newer targeted therapy drugs block specific enzymes or growth factor receptors (GFRs) found on many cancer cells. The monoclonal antibody trastuzumab (Herceptin) does this by blocking the effects of the growth factor receptor protein HER2. Because the HER2 protein transmits growth signals to breast cancer cells, trastuzumab is an active drug in the 25 percent of breast cancer patients who have too much HER2. In metastatic breast cancer, trastuzumab can be given as a single agent, but it is usually used initially with traditional chemotherapy drugs like paclitaxel. EGFR (epidermal growth factor receptor) is a protein receptor that, when stimulated sends out signals that trigger a series of chemical reactions that cause cancer cells to divide and multiply without control. The body’s natural immune system is unable to block this uncontrolled growth effectively. These signals also increase the blood supply to the tumor (angiogenesis) allowing more nutrients to reach the cancer cells and enabling them to grow even more. These signals also help the cancer cells to spread (metastasize) to distant sites in the body. These receptor sites (including HER1 and HER2) and chemical reactions present targets for other cancer treatment drugs like the monoclonal antibodies erlotinib (Tarceva), gefitinib (Iressa), and cetuximab (Erbitux). So far, research has failed to show these to have significant anti-breast cancer activity, but new studies are underway to see if, like trastuzumab (Herceptin), they are more useful when combined with standard cytotoxic chemotherapy drugs. Lapatinib (Tykerb) is a small molecule that inhibits HER2 proteins. Because it has a different mechanism of action than trastuzumab, lapatinib is useful in patients with HER2-positive breast cancer whose breast cancer has progressed following treatment on anthracycline, taxane, and trastuzumab. Unlike trastuzumab, it is an oral drug. It is usually given in combination with capecitabine.
Bevacizumab (Avastin) specifically inhibits vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the life cycle of a tumor. By inhibiting VEGF, bevacizumab is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize). Oncologists do give it as a single agent, but more typically, they initiate treatment by combining it with a traditional chemotherapy drug like paclitaxel, docetaxel, or capecitabine.
I have been taking trastuzumab (Herceptin), but the doctor says that my cancer is not responding to this treatment anymore. Do I have any other options?
Until recently, standard anti-cancer agents were the only option for women with HER2-positive breast cancer that stopped responding to trastuzumab. Now, there is a new HER2 receptor target drug, lapatinib (Tykerb), which may slow the growth of HER2-positive breast cancer metastases. Because it has a different mechanism of action than trastuzumab, lapatinib is useful in patients with HER2-positive breast cancer whose breast cancer has progressed following treatment with trastuzumab. A recent study showed that almost twice as many patients getting lapatinib with capecitabine responded to treatment than those receiving capecitabine alone. Those receiving the combination also stayed in remission longer. Both lapatinib and capecitabine are taken by mouth.
Antibodies- Special proteins produced by your immune system. They help protect the body from disease.
Immunohistochemistry (IHC) - The most commonly used test to see if a tumor has too much of the HER2 receptor protein on the surface of the cancer cells. The IHC test gives a score of 0 to 3+ that indicates the amount of HER2 receptor protein. It also measures the presence of hormone receptors on the breast cancer cell too and determines if a tumor is hormone receptor positive or negative.
Fluorescence in situ–hybridization (FISH) - This is a lab test that measures the amount of a certain gene in cells. It can be used to see if an invasive cancer has too many HER2 genes. A cancer with too many of these genes is called HER2-positive.
Drugs that target the hormone (estrogen and progesterone) receptors found on many breast cancer cells are among the oldest forms of breast cancer treatment.