CYP2D6 genotyping and the use of tamoxifen in breast cancer.

@article{Berry2013CYP2D6GA,
  title={CYP2D6 genotyping and the use of tamoxifen in breast cancer.},
  author={Donald A. Berry},
  journal={Journal of the National Cancer Institute},
  year={2013},
  volume={105 17},
  pages={
          1267-9
        }
}
  • D. Berry
  • Published 4 September 2013
  • Medicine, Biology
  • Journal of the National Cancer Institute
Donald Berry in his recent editorial (1) regarding the role of CYP2D6 and tamoxifen highlights several controversies that exist in the clinical and biomarker field for women with breast cancer. The International Tamoxifen Pharmacogenomics Consortium (ITPC) was formed with the intent to aggregate, curate, and analyze the data available in published breast cancer studies with the hope of answering the question, “Should CYP2D6 genotyping guide the use of tamoxifen in breast cancer?” The ITPC… 
Re: CYP2D6 genotyping and the use of tamoxifen in breast cancer.
Donald Berry in his recent editorial (1) regarding the role of CYP2D6 and tamoxifen highlights several controversies that exist in the clinical and biomarker field for women with breast cancer. The
CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast cancer.
  • P. Damkier
  • Medicine
    British journal of clinical pharmacology
  • 2014
TLDR
Despite the authors' introductory acknowledgement of an ongoing controversy, the uninitiated reader is left with the impression that the pro et contra of CYP2D6 genotyping prior to tamoxifen treatment in postmenopausal breast cancer, is now settled once and for all in favour of the pro.
Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics.
Effects of Pharmacogenetics on the Pharmacokinetics and Pharmacodynamics of Tamoxifen
TLDR
It is implied that tailored tamoxifen treatment may not be fully realized through pharmacogenetics of metabolizing enzymes alone, and the clinical implications of its findings are reviewed.
CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast cancer - a reply.
TLDR
The available evidence of the prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer is summarized and Damkier takes the position that the authors failed to discuss original findings by others.
Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.
TLDR
The concordance between CYP2D6 genotypes generated using 3 tissue sources (FFPETs; formalin-fixed, paraffin-embedded unaffected lymph nodes [FFPELNs]; and whole blood cells [WBCs]) from 122 breast cancer patients was determined and it was concluded that CYP 2D6genotypes obtained from FFPETs accurately represent the patient's CYP1D6 metabolic phenotype.
CYP2D6 Genotype and Adjuvant Tamoxifen
  • D. Berry
  • Medicine, Biology
    Clinical pharmacology and therapeutics
  • 2014
TLDR
An overall assessment of the evidence regarding testing for CYP2D6 in making clinical decisions regarding the use of tamoxifen in adjuvant breast cancer is provided.
CYP2D6 Genotype and Tamoxifen: Considerations for Proper Nonprospective Studies
TLDR
The ITPC analyses provided clear insights into the importance of quality control in considering the essential factors that are necessary to answer this pharmacogenetic question and, by extension, the precautions that must be considered for proper retrospective and “prospective– retrospective” studies.
Breast cancer recurrence in relation to antidepressant use
TLDR
Antidepressants overall, tricyclic antidepressants, and selective serotonin reuptake inhibitors were not associated with risk of breast cancer recurrence or mortality and there was some suggestion of an increased recurrence risk with concurrent paroxetine and tamoxifen use.
The Japanese Breast Cancer Society Clinical Practice Guideline for systemic treatment of breast cancer, 2015 edition
We have prepared the Japanese Breast Cancer Society clinical practice guidelines (CPGs) for surgical treatment of breast cancer, 2018 update after a systematic review (SR) of the literature based
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References

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Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters.
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  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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TLDR
The hypothesis of whether genetic polymorphisms of CYP2D6 can affect treatment outcome in patients with early postmenopausal breast cancer is revisited, comment on the complementary evidence, and discuss pros and cons of the validity of CYD6 tamoxifen pharmacogenetics.
Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial and Re: CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients.
TLDR
A major limitation of both new studies is the use of tumor DNA to determine germline genotype, and it is believed that purely observational studies may have equally good standardization of the population of interest and the outcome of interest.
CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients.
TLDR
The hypothesis that CYP2D6 genotype predicts clinical benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer patients is not supported.
Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes.
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  • Biology, Medicine
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TLDR
In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with the previous observation that CYP3A5*3 variant was not associated with any of these clinical outcomes.
CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial.
TLDR
The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen and support the hypothesis that reduced enzyme activity was associated with worse disease control.
CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment.
TLDR
Interactions between CYP2D6 polymorphisms and coadministered antidepressants and other drugs that are CYP 2D6 inhibitors may be associated with altered tamoxifen activity.
Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the Breast International Group 1-98 trial.
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TLDR
The genotype frequencies reported by regan et al. are highly implausible and the depletion of heterozygotes is likely attributable, at least in part, to the use of tumor DNA, which would entail highly unlikely intragenic rearrangements.
Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.
TLDR
The concordance between CYP2D6 genotypes generated using 3 tissue sources (FFPETs; formalin-fixed, paraffin-embedded unaffected lymph nodes [FFPELNs]; and whole blood cells [WBCs]) from 122 breast cancer patients was determined and it was concluded that CYP 2D6genotypes obtained from FFPETs accurately represent the patient's CYP1D6 metabolic phenotype.
Systematic Reviews on Selected Pharmacogenetic Tests for Cancer Treatment: CYP2D6 for Tamoxifen in Breast Cancer, KRAS for anti-EGFR antibodies in Colorectal Cancer, and BCR-ABL1 for Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
TLDR
This Technology Assessment assesses the evidence on the benefits and harms of three pharmacogenetic tests employed for three different diseases pertinent to the Medicare beneficiary population.
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