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. 2014 Aug 5;15(1):84–94. doi: 10.1038/tpj.2014.34

Table 4. Cox proportional hazard models of DRFS for (Z)-endoxifen plasma levels, MR DM-Tam/(Z)-endoxifen or CYP2D6 activity score/phenotype.

Quantitative analyses Categorical analyses  
 
 HR (per unit)a
 95% CI
 Wald P
  
 Factor
 HR
 95% CI
 Wald P
(Z)-Endoxifen (nM)       (Z)-Endoxifen (nM) >35 1 (Reference)    
 Unadjusted 0.989 0.973–1.004 0.142   24.7–35 1.61 0.76–3.38 0.210
 Adjusted 0.992 0.977–1.007 0.291   14.15–24.7 1.45 0.69–3.06 0.329
          <14.15 1.94 0.96–3.93 0.064
         Nodal status Negative 1 (Reference)    
          Positive 2.09 1.11–3.92 0.022
         Chemotherapy No 1 (Reference)   0.243
          Yes 1.65 0.71–3.83  
MR DM-Tam/(Z)-Endoxifen       MR DM-Tam/(Z)-Endoxifen <31 1 (Reference)    
 Unadjusted 1.008 1.001–1.015 0.025   31–115 1.43 0.86–2.37 0.167
 Adjusted 1.007 1.000–1.014 0.036   >115 3.82 1.47–9.89 0.006
         Nodal status Negative 1 (Reference)    
          Positive 2.09 1.12–3.89 0.021
         Chemotherapy No 1 (Reference)    
          Yes 1.62 0.70–3.74 0.260
CYP2D6 activity score       CYP2D6 phenotype class EM/UM 1 (Reference)    
 Unadjusted 0.611 0.425–0.88 0.008   hetEM/IM 1.55 0.88–2.72 0.132
 Adjusted 0.623 0.429–0.905 0.013   PM 1.98 0.82–4.79 0.128
         Nodal status Negative 1 (Reference)    
          Positive 2.15 1.14–4.04 0.018
         Chemotherapy No 1 (Reference)    
          Yes 1.60 0.69–3.73 0.277

Abbreviations: CI, confidence interval; DRFS, distant recurrence-free survival; HR, hazard ratio; MR DM-Tam/(Z)-endoxifen, metabolic ratio N-desmethyltamoxifen/(Z)-endoxifen; TAM, tamoxifen.

Node status was binary coded with factor levels negative vs positive; chemotherapy was binary coded with levels no (no chemotherapy given) and yes (chemotherapy given); CYP2D6 and tamoxifen metabolite predictor variables were coded categorically. Models were corrected for nodal status and chemotherapy and stratified for ethnicity.

a

For univariate analysis, HR refers to an increase by one unit (1 nM) of steady-state endoxifen plasma concentration, increase of the dimensionless MR DM-Tam/(Z)-endoxifen ranging between 8 (highest) and 176 (lowest) endoxifen formation rates and an increase by one unit of CYP2D6 phenotype score ranging from 0 (PM) to 3 (UM).