Table 5. Mean concentrations of tamoxifen and its metabolites according to genotypes and predicted phenotypes.
| Variables (n) | Mean concentrations (95% CI) in ng/mL | |||||||
|---|---|---|---|---|---|---|---|---|
| Endoxifen | NDM | Tam | 4-OH Tam | Endoxifen /NDM | Endoxifen /4-OH Tam | NDM /Tam | 4-OH Tam /Tam | |
| CYP1A2 -2467delT | ||||||||
| TT (21) | 30.5 (25.2-35.8) |
243 (209-276) |
149 (125-172) |
10.3 (8.78-11.9) |
0.13 (0.11-0.15) |
3.03 (2.64-3.42) |
1.68 (1.54-1.82) |
0.07 (0.06-0.08) |
| T- + -- (59) | 25.3 (22.8-27.8) |
225 (195-254) |
123 (110-137) |
9.27 (8.64-9.90) |
0.14 (0.12-0.17) |
2.83 (2.56-3.11) |
1.80 (1.69-1.91) |
0.08 (0.08-0.09) |
| P | 0.043a (0.011)b (0.048)c |
0.503 | 0.062 (0.108) |
0.125 | 0.899 | 0.303 | 0.216 | 0.066 (0.314) |
| CYP2B6 genotype | ||||||||
| NF/IOF (8) | 20.5 (15.0-26.1) |
216 (162-270) |
123 (87.0-158) |
7.20 (4.45-9.95) |
0.10 (0.06-0.14) |
3.44 (1.91-4.96) |
1.79 (1.62-1.95) |
0.06 (0.03-0.09) |
| NF/NF (52) | 27.2 (24.3-30.0) |
238 (207-268) |
133 (120-146) |
9.69 (9.06-10.3) |
0.14 (0.11-0.17) |
2.86 (2.59-3.12) |
1.77 (1.65-1.89) |
0.08 (0.07-0.08) |
| NF/DOF (14) | 30.1 (22.9-37.2) |
244 (185-302) |
146 (104-187) |
11.0 (8.93-13.0) |
0.14 (0.10-0.18) |
2.76 (2.31-3.21) |
1.76 (1.57-1.94) |
0.09 (0.07-0.10) |
| DOF/DOF (1) | 27.6 | 265 | 109 | 9.80 | 0.10 | 2.82 | 2.43 | 0.09 |
| P | 0.031 (0.077) (0.487) |
0.539 | 0.429 | 0.005 (0.004) (0.002) |
0.335 | 0.361 | 0.654 | 0.039 (0.628) |
| CYP2D6 AS | ||||||||
| 2 (19) | 30.1 (24.8-35.4) |
184 (145-223) |
116 (87.8-144) |
10.2 (8.75-11.6) |
0.19 (0.15-0.23) |
2.94 (2.66-3.22) |
1.63 (1.48-1.78) |
0.10 (0.09-0.11) |
| 1.5 (37) | 27.1 (23.5-30.7) |
234 (197-270) |
138 (120-155) |
9.54 (8.59-10.5) |
0.14 (0.11-0.17) |
2.95 (2.60-3.30) |
1.68 (1.57-1.80) |
0.07 (0.07-0.08) |
| 1 (20) | 24.0 (19.9-28.2) |
254 (209-300) |
132 (109-155) |
9.30 (8.22-10.4) |
0.11 (0.07-0.16) |
2.73 (2.15-3.32) |
1.93 (1.78-2.09) |
0.08 (0.07-0.08) |
| 0.5 (4) | 19.5 (17.2-21.7) |
283 (77.3-489) |
119 (65.9-171) |
7.90 (3.72-12.1) |
0.08 (0.04-0.12) |
2.78 (0.75-4.81) |
2.39 (1.26-3.52) |
0.07 (0.03-0.11) |
| P | 0.009 (0.004) (< 0.001) |
0.018 (0.012) (< 0.001) |
0.581 | 0.132 | < 0.001 (< 0.001) |
0.181 | < 0.001 (< 0.001) |
0.010 (0.005) |
| FMO3 441C>T | ||||||||
| CC (48) | 27.0 (23.4-30.6) |
206 (182-230) |
122 (107-136) |
9.26 (8.39-10.1) |
0.15 (0.12-0.19) |
3.04 (2.69-3.39) |
1.73 (1.61-1.84) |
0.08 (0.07-0.09) |
| CT + TT (32) | 26.2 (23.8-28.6) |
265 (221-309) |
143 (123-163) |
9.99 (9.17-10.8) |
0.12 (0.10-0.14) |
2.65 (2.45-2.86) |
1.83 (1.70-1.97) |
0.08 (0.07-0.08) |
| P | 0.802 | 0.013 (0.002) (0.027) |
0.076 (0.139) |
0.242 | 0.063 (0.134) |
0.141 | 0.237 | 0.298 |
| SULT1E1 -9-899G>A | ||||||||
| GG (48) | 26.6 (23.8-29.5) |
252 (219-285) |
139 (122-156) |
9.76 (8.89-10.6) |
0.12 (0.11-0.14) |
2.83 (2.55-3.11) |
1.83 (1.72-1.95) |
0.08 (0.07-0.08) |
| GA (27) | 26.9 (22.2-31.6) |
200 (172-228) |
120 (107-133) |
9.28 (8.32-10.2) |
0.16 (0.11-0.21) |
3.00 (2.54-3.47) |
1.67 (1.51-1.83) |
0.08 (0.07-0.09) |
| AA (5) | 25.4 (13.9-36.9) |
171 (15.1-326) |
99.4 (12.4-186) |
8.96 (6.72-11.2) |
0.19 (0.06-0.32) |
2.79 (2.04-3.55) |
1.70 (1.33-2.08) |
0.11 (0.06-0.17) |
| P | 0.881 | 0.014 (0.005) (0.190) |
0.045 (0.014) |
0.383 | 0.022 (0.180) |
0.636 | 0.117 | 0.022 (0.006) |
| SULT1E1 -9-899G>A | ||||||||
| GG (48) | 26.6 (23.8-29.5) |
252 (219-285) |
139 (122-156) |
9.76 (8.89-10.6) |
0.12 (0.11-0.14) |
2.83 (2.55-3.11) |
1.83 (1.72-1.95) |
0.08 (0.07-0.08) |
| GA+AA (32) | 26.7 (22.6-30.8) |
195 (167-224) |
117 (102-131) |
9.23 (8.40-10.1) |
0.16 (0.12-0.21) |
2.97 (2.57-3.37) |
1.67 (1.53-1.81) |
0.09 (0.08-0.10) |
| P | 0.967 | 0.015 | 0.068 | 0.399 | 0.038 | 0.530 | 0.076 (0.049) |
0.141 |
| SULT1E1 -9-682A>G | ||||||||
| AA (67) | 27.3 (24.7-30.0) |
234 (208-259) |
130 (117-143) |
9.58 (8.91-10.3) |
0.14 (0.12-0.16) |
2.94 (2.68-3.20) |
1.81 (1.71-1.91) |
0.08 (0.07-0.09) |
| AG + GG (12) | 23.1 (19.4-26.8) |
209 (140-277) |
131 (89.4-172) |
9.35 (7.50-11.2) |
0.14 (0.09-0.18) |
2.60 (2.08-3.12) |
1.59 (1.46-1.71) |
0.08 (0.06-0.10) |
| P | 0.199 | 0.444 | 0.971 | 0.784 | 0.915 | 0.216 | 0.078 (0.017) |
0.841 |
| SULT1E1 -9-469A>G | ||||||||
| AA+AG (69) | 26.8 (24.2-29.3) |
221 (196-247) |
127 (114-139) |
9.44 (8.76-10.1) |
0.15 (0.12-0.17) |
2.94 (2.69-3.20) |
1.75 (1.65-1.84) |
0.08 (0.08-0.09) |
| GG (11) | 25.9 (20.4-31.5) |
281 (227-334) |
152 (120-183) |
10.2 (9.03-11.4) |
0.10 (0.07-0.13) |
2.51 (2.19-2.84) |
1.90 (1.65-2.15) |
0.07 (0.06-0.08) |
| P | 0.950 | 0.077 (0.451) (0.251) |
0.148 | 0.380 | 0.059 (0.019) |
0.195 | 0.220 | 0.245 |
| UGT2B7 genotype | ||||||||
| *1/*1 (28) | 28.4 (23.7-33.0) |
231 (180-282) |
135 (112-158) |
10.2 (9.07-11.4) |
0.15 (0.12-0.19) |
2.73 (2.47-2.99) |
1.69 (1.50-1.88) |
0.08 (0.07-0.09) |
| *1/*2, *1/*3 (35) | 26.4 (22.8-30.0) |
236 (210-262) |
132 (118-146) |
9.02 (8.07-9.98) |
0.13 (0.09-0.16) |
3.15 (2.70-3.60) |
1.81 (1.70-1.92) |
0.07 (0.06-0.08) |
| *2/*3, *3/*3 (6) | 20.5 (13.7-27.4) |
158 (92.7-224) |
80.7 (53.7-108) |
8.38 (7.36-9.41) |
0.16 (0.05-0.27) |
2.44 (1.79-3.09) |
1.93 (1.52-2.33) |
0.11 (0.08-0.15) |
| P | 0.145 | 0.329 | 0.080 (0.186) |
0.057 (0.020) (0.122) |
0.583 | 0.818 | 0.135 | 0.429 |
AS, activity score; BMI, body mass index; CI, confidence interval; NDM, N-desmethyltamoxifen; 4-OH Tam, 4-hydroxytamoxifen; Tam, tamoxifen.
aUnivariable p-value.
bMultivariable p-value.
cP-value from multivariable analysis including tamoxifen concentration as indicator for compliance and drug absorption.