kat in the delta
02-07-2008, 02:48 PM
How many of you ..have had a genetic test ?
Did your insurance cover the cost?
Did it save you from UNNECESSARY CHEMOS ??
Who has had the Oncotype test..or is this one in the same ??
.....and would you recommend this after a yr..since treatments if you wanted to have reconstruction on one breast ????
==============Kat in the delta
02-22-2008, 01:47 PM
Depends on what you mean by "unnecessary chemos." Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. A molecular-targeted breast prognostic test like Oncotype DX enables the oncologist and breast cancer surgeon to more accurately determine who should be treated and who should not be treated with chemotherapy, but they cannot predict chemo response!
In chemotherapy selection, Gene and Protein testing examine a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response. Functional profiling tests not only for the presence of genes and proteins but also for their functionality, for their interaction with other genes, proteins, and processes occurring within the cell, and for their response to anti-cancer drugs.
These genetic tests to identify molecular predisposing mechansims still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.
Gene profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, are still years away from working successfully in predicting treatment response for "individual" patients. Perhaps this is because they are performed on dead, preserved cells that were never actually exposed to the drugs whose activity they are trying to assess.
The key to understanding the genome is understanding how cells work. The ultimate driver is a "functional" assay (is the cell being killed regardless of the mechanism) as opposed to a "target" assay (does the cell express a particular target that the drug is supposed to be attacking). While a "target" assay tells you whether or not to give "one" drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay.
Cell-based functional assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on functional behavior not available in any other kind of assays.
The "forest and trees" analogy can explained the fact that conventional chemo treatments try to kill "all" cancerous cells (along with non-cancerous cells). The whole forest of cells. The new "targeted" drugs go after a "pathway" within or on cancerous cells. Hence the "trees" instead of the "forest."
With "functional" cell-based assays, the "forest" is looked at and not the "trees." There are many pathways to altered cellular (forest) function (hence all the different "trees" which correlate in different situations). The "functional" profiling technique of cell-death assays, measures what happens at the end (the effects on the forest), rather than the status of the individual trees. Cancer is a complex disease and needs to be attacked on many fronts.
Cancer therapy needs to be thought of "outside the box" with "personalized" treatments for "individual" patients, and requires a combination of novel diagnostics and therapeutics. If "some" drugs are working for "some" people (not average populations), then obviously there are others out there who would also benefit. Who are those that would benefit? All the more reason to test the tumor first.
A cell culture assay with "functional" profiling, using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive). Cell "function" analysis doesn't claim to have a perfect model, but all retrospective studies have documented that killing cells in the test tube does correlate with dead cancer cells in the patient.
"Funtional" profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell (forest), resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected (trees), "functional" profiling is measuring them through the surrogate of measuring if the cell is alive or dead.
For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack.
It doesn't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.
In an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer. One-size-does-not-fit-all.
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