| Title |
The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, November 2006
|
| DOI | 10.1007/s10549-006-9428-0 |
| Pubmed ID | |
| Authors |
Matthew P. Goetz, Stacey K. Knox, Vera J. Suman, James M. Rae, Stephanie L. Safgren, Matthew M. Ames, Daniel W. Visscher, Carol Reynolds, Fergus J. Couch, Wilma L. Lingle, Richard M. Weinshilboum, Emily G. Barr Fritcher, Andrea M. Nibbe, Zeruesenay Desta, Anne Nguyen, David A. Flockhart, Edith A. Perez, James N. Ingle |
| Abstract |
Tamoxifen is biotransformed to the potent anti-estrogen, endoxifen, by the cytochrome P450 (CYP) 2D6 enzyme. CYP2D6 genetic variation and inhibitors of the enzyme markedly reduce endoxifen plasma concentrations in tamoxifen-treated patients. Using a North Central Cancer Treatment Group adjuvant tamoxifen trial, we performed a comprehensive evaluation of CYP2D6 metabolism by assessing the combined effect of genetic variation and inhibition of the enzyme system on breast cancer recurrence and death. Medical records were reviewed at each randomizing site to determine whether CYP2D6 inhibitors were co-prescribed with tamoxifen. Extensive metabolizers were defined as patients without a *4 allele (i.e., wt/wt) who were not co-prescribed a CYP2D6 inhibitor. Patients with decreased CYP2D6 metabolism were classified as intermediate or poor metabolizers (PM) based on the presence of one or two CYP2D6*4 alleles or the co-administration of a moderate or potent CYP2D6 inhibitor. The association between CYP2D6 metabolism and clinical outcome was assessed using Cox modeling. Medication history was available in 225/256 eligible patients and CYP2D6*4 genotype in 190 patients. Thirteen patients (6%) were co-prescribed a CYP2D6 inhibitor [potent (n = 3), moderate (n = 10)], resulting in the following CYP2D6 metabolism: extensive (n = 115) and decreased (n = 65). In the multivariate analysis, patients with decreased metabolism had significantly shorter time to recurrence (p = 0.034; adj HR = 1.91; 95% CI 1.05-3.45) and worse relapse-free survival (RFS) (p = 0.017; adj HR = 1.74; 1.10-2.74); relative to patients with extensive metabolism. Cox' modeling demonstrated that compared to extensive metabolizers, PM had the most significant risk of breast cancer relapse (HR 3.12, p = 0.007). CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer. Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women. |
Mendeley readers
The data shown below were compiled from readership statistics for 166 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | <1% |
| Sweden | 1 | <1% |
| United Kingdom | 1 | <1% |
| Canada | 1 | <1% |
| Japan | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 160 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 30 | 18% |
| Student > Ph. D. Student | 25 | 15% |
| Researcher | 22 | 13% |
| Student > Bachelor | 17 | 10% |
| Professor | 10 | 6% |
| Other | 35 | 21% |
| Unknown | 27 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 44 | 27% |
| Biochemistry, Genetics and Molecular Biology | 26 | 16% |
| Agricultural and Biological Sciences | 20 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 16 | 10% |
| Chemistry | 9 | 5% |
| Other | 22 | 13% |
| Unknown | 29 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 22. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 December 2021.
All research outputs
#1,438,569
of 22,950,943 outputs
Outputs from Breast Cancer Research and Treatment
#178
of 4,670 outputs
Outputs of similar age
#4,215
of 154,890 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#1
of 27 outputs
Altmetric has tracked 22,950,943 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,670 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 154,890 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.