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Pitfalls and shortcomings of pharmacogenomic association studies: The tamoxifen controversy
Published on Jul 21, 20141679 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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Chapter list
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