HER2 Support Group Forums - View Single Post - Genomic Test Shows Promise As Predictor Of Chemotherapy Response, Survival For Women

gdpawel · 08-04-2013, 05:15 PM

In this prospective study, genomic testing that was prognostic for response to anthracycline and taxane therapy in women with newly diagnosed invasive breast cancer was shown to have improved on predictions based on clinicopathologic parameters.

Here's the fatal flaw: It's just like all similar studies (including OncotypeDX). It's not a real world situation. What they are doing is to collect and freeze specimens and batch process them. This is similar to virtually all of the breast cancer studies, using IHC for ER and Her2 (where studies are performed by batch processing archival, paraffin-embedded specimens).

This is not real world, in which specimens are received daily, in real time, and processed in a clinically relevant time frame. In the real world, when patient gets a biopsy, the specimen gets processed and reported within a few days to a couple of weeks. Each specimen is processed and tested individually, by whomever happens to be working on the days in question. It's not the same team of technicians, working with the same pathologist, with the same reagents and the same microarrays, doing it all at the same time.

With cell culture assays, it is a real world situation. Specimens are received over days, weeks, months, years. They are processed and completed as they come in through the door.

With the NEJM OncotypeDX study, all of the specimens were batched processed within the same 2 week time segment (for hundreds of specimens). Had the specimens been processed and studied under real world conditions (months and years), the correlations would certainly not have been nearly as good.

The same thing goes with ER and Her2. These are "batch processed" studies. This is the only study of which there was reasonably real world (specimens processed and tests completed as specimens were received). Note the poor correlations, particularly with regard to false negatives.

I don't know how one could really deny any breast cancer patient with metastatic disease a trial of hormonal therapy, given the 20% response rate for ER negative patients, with ER performed using IHC in "real world" conditions. But we think that ER negative patients have only a 10% or less response rate, based entirely on non-real world "batch processed" studies.

But that's how all these multi-gene studies are done. Batch processed and retrospective. Utterly non-real world.

08-04-2013, 05:15 PM	#2
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	Fatal Flaw In this prospective study, genomic testing that was prognostic for response to anthracycline and taxane therapy in women with newly diagnosed invasive breast cancer was shown to have improved on predictions based on clinicopathologic parameters. Here's the fatal flaw: It's just like all similar studies (including OncotypeDX). It's not a real world situation. What they are doing is to collect and freeze specimens and batch process them. This is similar to virtually all of the breast cancer studies, using IHC for ER and Her2 (where studies are performed by batch processing archival, paraffin-embedded specimens). This is not real world, in which specimens are received daily, in real time, and processed in a clinically relevant time frame. In the real world, when patient gets a biopsy, the specimen gets processed and reported within a few days to a couple of weeks. Each specimen is processed and tested individually, by whomever happens to be working on the days in question. It's not the same team of technicians, working with the same pathologist, with the same reagents and the same microarrays, doing it all at the same time. With cell culture assays, it is a real world situation. Specimens are received over days, weeks, months, years. They are processed and completed as they come in through the door. With the NEJM OncotypeDX study, all of the specimens were batched processed within the same 2 week time segment (for hundreds of specimens). Had the specimens been processed and studied under real world conditions (months and years), the correlations would certainly not have been nearly as good. The same thing goes with ER and Her2. These are "batch processed" studies. This is the only study of which there was reasonably real world (specimens processed and tests completed as specimens were received). Note the poor correlations, particularly with regard to false negatives. I don't know how one could really deny any breast cancer patient with metastatic disease a trial of hormonal therapy, given the 20% response rate for ER negative patients, with ER performed using IHC in "real world" conditions. But we think that ER negative patients have only a 10% or less response rate, based entirely on non-real world "batch processed" studies. But that's how all these multi-gene studies are done. Batch processed and retrospective. Utterly non-real world.