Re: CYP2D6 Genotype Not Found To Predict Tamoxifen Benefit In Breast Cancer
It was hoped that Genomic Analyses of cancer tumors would be able to identify in advance which patients will benefit from the use of cancer drugs (clinical responders). The Agency for Healthcare Research and Quality (AHRQ) questioned this a few years ago, with the finding that there was "no consistent associations" between breast cancer patients with the relevant CYP2D6 (genotype) polymorphism and the outcome of tamoxifen therapy, whether as primary treatment or in post-operative adjuvant therapy.
As is often the case, the numerous studies identified by a systematic review didn't contain enough data to draw definitive conclusions. Most studies were relatively small and thus underpowered to detect what would be a plausible effect size for the modification or response to tamoxifen by a single polymorphism. In addition, one of the studies showed that CYP2D6 genotypes with reduced enzyme activity are not linked to fewer tamoxifen-induced hot flushes.
This doesn't surprise me and I can empathize with the frustration. There virtually hasn't been any progress at all in drug selection through the use of molecular profiling. When microarrays and high throughput RT-PCR emerged some years back, you'd think that there would be quite a bit of progress. Sad to say, there has not. Genetic variations alone can not determine response to therapy. Genotype analysis is strictly theoretical.
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