FISH Technology Preferred For Choosing HER-2-Positive Breast Cancer Treatments

[gdpawel]

Recent research has shown that the best way to determine whether a tumor will respond to Herceptin is to look at whether it overexpresses the Her2/neu oncogene, not whether it is making too much Her2/neu protein. And the best way to examine the oncogenes is with FISH (Fluorescence In Situ Hybridization). Because the results of the IHC test can sometimes be ambiguous, many doctors suggest the FISH test for a second opinion.

Tumors that are 3+ positive by IHC and those that test positive by FISH are most likely to benefit from Herceptin. Tumors that test 1+ by IHC are considered Her2/neu negative and those that test 2+ are considered equivical, in which case FISH testing is done to make the determination. Tumors that test negative for Her2/neu by FISH are unlikely to benefit from Herceptin.

Previous studies demonstrated that there is poor agreement between the results from local laboratory-based Her2/neu testing and those of central testing by experienced investigators. There has been poor concordance between community and central laboratory testing, in terms of both Her2 protein expression and gene amplification. Even still, there has been poor concordance in terms of FISH testing in a central laboratory compared to local laboratories, which the prevalent notion regarding FISH is that it is 100% accurate.

However, it doesn't matter if there is a "target" molecule (gene or protein) in the cell that the targeted drug is going after, if the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial. The advantage of cell-based functional profiling is that it can show this in the "population" of cells (entire genome).

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 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 targeted drug with other types of conventional cancer drugs. So far, cell-based functional profiling has demonstrated this critical ability.

Source: Cell Function Analysis