TABLE 21Summary of endoxifen concentrations in relation to CYP2D6 status by genotype

Cohort/studyAlleles testedSummary of findings
Stearns et al. 200349*4, *6, *8Decrease in endoxifen concentrations after taking the CYP2D6 inhibitor paroxetine:

wt/wt genotype: 64% (95% CI 39% to 89%)

wt/vt or vt/vt genotype: 24% (95% CI 23% to 71%)

p = 0.03

Where vt = *4, *6, *8

Baseline plasma endoxifen concentrations were lower in women with *4, *6 or *8 alleles than in those with wt (p = 0.002)
Henry et al. cohort:87

Jin et al. 2005105
*3, *4, *5, *6Mean (range) endoxifen plasma concentrations, ng/ml:

wt/wt: 78.0 (65.9 to 90.1)

wt/vt: 43.1 (33.3 to 52.9)

vt/vt: 20.0 (11.1 to 28.9)

p < 0.01

vt = * 3, *4, *5, *6
Lim et al. 200773*5, *10, *2 × NMean (range) endoxifen plasma concentrations, ng/ml:

wt/wt (n = 64): 19.9 (18.0 to 21.9)

wt/*10 (n = 89): 18.1 (16.8 to 19.5)

*10/*10 (n = 49): 7.9 (7.1 to 8.8)

p < 0.0001

Where wt = allele not containing *10

Mean (range) endoxifen plasma concentrations, ng/ml:

wt/wt: (n = 55): 20.7 (18.5 to 22.9)

wt/vt (n = 96): 18.0 (16.7 to 19.2)

vt/vt (n = 51): 8.1 (7.2 to 9.0)

p < 0.0001

Where wt = allele not containing *5 and *10
Kiyotani et al. cohort:114

Kiyotani et al. 2010114
*4, *5, *6, *10, *14, *18, *21, *36, *41Median endoxifen plasma concentrations, ng/ml:

wt/wt (n = 24): 35.4

wt/vt (n = 45): 27.2

vt/vt (n = 29): 15.5

N, number of copies of the allele.

From: 3, Assessment of clinical effectiveness

Cover of The Clinical Effectiveness and Cost-Effectiveness of Genotyping for CYP2D6 for the Management of Women with Breast Cancer Treated with Tamoxifen: A Systematic Review
The Clinical Effectiveness and Cost-Effectiveness of Genotyping for CYP2D6 for the Management of Women with Breast Cancer Treated with Tamoxifen: A Systematic Review.
Health Technology Assessment, No. 15.33.
Fleeman N, Saborido CM, Payne K, et al.
Southampton (UK): NIHR Journals Library; 2011 Sep.
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