Impaired Tamoxifen Metabolism Reduces Survival in Familial Breast Cancer Patients

@article{Newman2008ImpairedTM,
  title={Impaired Tamoxifen Metabolism Reduces Survival in Familial Breast Cancer Patients},
  author={William G. Newman and Kristen D. Hadfield and Ayshe Latif and Stephen A. Roberts and Andrew Shenton and Christopher McHague and Fiona Lalloo and Sacha J. Howell and D. Gareth R. Evans},
  journal={Clinical Cancer Research},
  year={2008},
  volume={14},
  pages={5913 - 5918}
}
Purpose: Tamoxifen has been the mainstay adjuvant hormonal treatment for breast cancer for many years. Conversion of tamoxifen to its active metabolite, endoxifen, is reduced by low activity of the cytochrome P450 enzyme, CYP2D6. We examined the effect of reduced CYP2D6 activity on the response to tamoxifen in patients with familial early-onset breast cancer. Experimental Design: We conducted a case note review and genotyping for the CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*41 alleles in 115… 
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The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer
TLDR
CYP2D6 phenotype is an important predictor of treatment outcome in women who are receiving tamoxifen for MBC and should therefore be handled with care.
Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes.
CYP2D6 Polymorphisms and Tamoxifen Metabolism: Clinical Relevance
TLDR
The balance of current evidence strongly suggests that the presence of two wild-type alleles, and possibly one null allele, predicts reduced tamoxifen metabolism and an inferior outcome in postmenopausal women with early breast cancer who receive adjuvant treatment with the drug.
CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen.
TLDR
The hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen is investigated.
Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment
TLDR
The present analysis suggests that CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients.
Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.
TLDR
The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome.
Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer
TLDR
The results show a significant influence of the CYP2D6 genotype on the efficacy of Tam in the treatment of ABC, and the evidence in the palliative setting is congruent.
Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype.
Pharmacogenetics of endocrine therapy for breast cancer.
TLDR
Emerging data suggest that host factors may also predict interpatient variability in response to aromatase inhibitors, and women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced activity may have an inferior breast cancer outcome when treated with tamoxifen in the adjuvant setting.
Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype.
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