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Pitfalls and shortcomings of pharmacogenomic association studies: The tamoxifen controversy
Published on 2014-07-211684 Views
The Cytochrome P450 2D6 enzyme has been linked with tamoxifen outcome based on its role to convert the parent drug into active metabolites 4-hydroxytamoxifen and endoxifen and in particular becaus
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Presentation
Pitfalls and shortcomings of pharmacogenomic association studies: The tamoxifen controversy00:00
Tamoxifenin early breast cancer00:55
Mechanisms of endocrine therapy in early BC01:35
Aromatase inhibitor versus tamoxifen outcome02:38
Tamoxifen is a prodrug03:15
Sparteine oxidation phenotypes and distributionin a German population04:02
Molecular Basis of the CYP2D6 Polymorphism04:25
Pharmacogenetics/ Pharmacogenomics04:43
CYP2D6 polymorphism and recurrence probabilities upon tamoxifen treatment - 104:49
CYP2D6 polymorphism and recurrence probabilities upon tamoxifen treatment - 205:05
The Tamoxifen benefit for patients with fully functiona CYP2D6 is similar as that of AI05:32
The Stuttgart –Mayo study cohort05:48
What level of evidence is needed?06:36
Highest level evidence was expected from prospective clinical trials07:01
Characteristics of Tamoxifen-CYP2D6-pharmacogenetics studies and pitfalls - 107:36
Characteristics of Tamoxifen-CYP2D6-pharmacogenetics studies and pitfalls - 208:28
Characteristics of Tamoxifen-CYP2D6-pharmacogenetics studies and pitfalls - 309:01
Loss of heterozygosity (LOH) is a hallmark of many cancers09:58
22q13 LOH is common in breast cancer10:41
Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Gremline DNA - 111:03
Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Gremline DNA - 211:19
The Cancer Genome Atlas (TCGA) Breast Data11:32
Attention must be paid whe ngenomic DNA is isolated for pharmacogenetic investigations12:13
Austrian ABCSG 8 Trial: Reduced CYP2D6 metabolism and highe rrisk for recurrence12:55
CYP2D6 genotype is associated with a higher risk of recurrence13:41
Variability of the (Z)-endoxifen plasma levels14:04
CYP2D6 and (Z)-endoxifen formation (N=236)14:43
Breast canceroutcomesin the WHEL study15:08
Tamoxifen Use in Postmenopausal Breast Cancer: CYP2D6 Matters15:41
Modeling the pharmacological importance of endoxifenfor the treatment of ER positive breast cancer in premenopausal women15:52
The premenopausal situation - 117:19
The premenopausal situation - 218:18
CYP2D6 predicts outcome in POSH - 118:32
CYP2D6 predicts outcome in POSH - 218:59
Impact of CYP2C19 and CYP2C9 on tamoxifen metabolite ratios19:22
Tamoxifen Pharmacogenetics19:39
Cancer Pharmacogenomic Study Design20:48
Lessons learned from pitfalls in tamoxifen pharmacogenomics - 121:11
Lessons learned from pitfalls in tamoxifen pharmacogenomics - 221:46
Lessons learned from pitfalls in tamoxifen pharmacogenomics - 322:07
Lessons learned from pitfalls in tamoxifen pharmacogenomics - 422:25
Thank you23:02