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Old 02-08-2006, 06:18 PM   #9
Lani
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apples and oranges (or FISH vs IHC and Ki67 vs mitotic index)

I will try to get the original article, but in the meantime it seems we are comparing apples and oranges. The method of her2 detection here was ihc ("immunohistochemistry"). There have been many studies showing that FISH is the more accurate method for detecting her2 overamplification and that a large percentage of ihc2+ tumors are, in fact, FISH negative. IT seems that Herceptin's effect is best in tumors which are FISH positive--the results in trial before FISH was used as the determinant of her positivity were considerably worse ie Herceptin does not work as well on IHC 2+ but FISH -patients.

Ki67 is generally felt to be the best test of proliferation ("mitotic index" means literally an index of how often the cells are dividing), but it is not done everywhere and not equally well everywhere.

Interestingly, in the development of the ONCODX test of the 21 genes chosen to evaluate --one was estrogen receptor, one was progesterone receptor, one was her2neu and a neighboring gene which almost always goes with it..the vast majority of the other genes were those indicating proliferation. Thus at San Antonio I heard it said by Dr. Slamon and others that one could save the $3500 by having a well-performed her2 by FISH, ER, PR and Ki67--perhaps RobinP's recommended company Targeted Molecular Diagnosistics could provide a second opinion service testing those 4 markers for less than their normal $190 per marker for those on this board. That would particularly help our non US members who have trouble convincing their doctors, or the National Health Service or equivalent, to test their tumor, or if they doubt the testing is done well locally.
The reason the ER and PR are important is that they are QUANTITATIVELY decreased in her2 + tumors ie their percentage may be high, but their absolute amount tends to be low which might become important in treatment choices.

To put Robins article in perspective--that was in 2003 in Italy. Those were the methods they were using then to test.

I hope we never again get studies with these sorts of figures--ie, that everyone with a her2 tumor will be treated with herceptin +/- chemotherapy or other systemic treatment rather than getting "locoregional treatment alone" (I think the thinking was that it was SIZE that mattered and small tumors just didn't need additional therapy--there are many on this website who have proven them wrong)

Thanks for all the info Robin!

Lani
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