Genetic Testing and Tailored Breast Cancer Treatment
Women with early-stage breast cancer may be eligible for a trial of TAILORx, the Trial Assigning IndividuaLized Options for Treatment (Rx). Treatments such as chemotherapy, radiation, and hormone suppression do benefit many patients, but do you need to take all of these? The results of a TAILORx test gives guidance for the answer that best suits you. This trial tests the tumor tissue sample for the production of 21 genes which may be causing the cancer. Each gene production is given a score. All of the gene scores are then plugged into a calculation which can show the chances of recurrence of the breast cancer, within 10 years of your initial diagnosis. Based on that result, your oncologist can help you make the best decision about your treatment plan.
Read about HER2, one gene that affects breast cancer.
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Over the past few years, researchers have put enormous efforts into genetic profiling as a way of predicting patient response to targeted therapies. However, no gene-based test has been described that can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can an available gene-based test identify situations in which it is advantageous to combine a tarteted drug with other types of cancer drugs. So far, only whole cell profiling has demonstrated this critical ability.
The EGFRx ™ assay will test molecularly-targeted anti-cancer drugs therapies like Iressa, Tarceva, Sutent and possibly Nexavar, because of being small molecules. The monoclonal antibodies like Herceptin and Erbitux are “enormous” molecules. These very large molecules don’t have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth.
However, drugs like Avastin (although a monoclonal antibody) can be tested with EGFRx ™ because the target of Avastin is not the cells themselves, but rather a hormone (VEGF) secreted by the tumor cells. The Avastin complexes with free VEGF and blocks its action. The EGFRx ™ test can discriminate between the activity of different targeted drugs and identify situations in which it is advantageous to combine the targeted drugs with other types of cancer drugs. All the more reason to “test the tumor first.”
Most patients are treated not with a targeted therapy drug alone but with a combination of chemotherapy drugs. Therefore, existing DNA and RNA tests do not reflect the way cancer medicine is practiced today. The EGFRx assay, developed by The Weisenthal Cancer Group relies upon a technique known as “Whole Cell Profiling” in which living tumour cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs.
A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient’s cancer cells. The whole cell profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic and morphologic endpoints. Other tests, such as those which identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process.
Not only is this an important predictive test that is available “today,” but it is also a unique tool that can help to identify newer and better drugs, evaluate promising drug combinations, and serve as a “gold standard” correlative model with which to develop new DNA, RNA, and protein-based tests that better predict for drug activity.
These “targeting” drugs are expensive, costing patients and insurance carriers $5,000 to $7,000 or more per month of treatment. Patients, physicians, insurance carriers, and the FDA are all calling for the discovery of predictive tests that allow for rational and cost-effective use of these drugs.
The whole cell profiling approach, holds the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them.