Table 2. . Association of activity phenotype with anastrozole and fulvestrant systemic concentrations.
| Gene | Comparison | Anastrozole systemic concentration† (n = 79) | Fulvestrant systemic concentration (n = 52) | ||
|---|---|---|---|---|---|
| β (95% CI) | p-value | β (95% CI) | p-value | ||
| CYP3A4 | PM/IM vs NM | 5.8 (91.6, 13.2) | 0.13 | 0.1 (-1.6, 1.9) | 0.88 |
| CYP3A5 | PM vs IM/NM | 1.1 (-1.6, 13.2) | 0.77 | 0.1 (-1.3, 1.5) | 0.84 |
| ABCB1 | PM vs IM/NM | 1.2 (-4.9, 7.3) | 0.70 | 0.4 (-0.6, 1.5) | 0.43 |
| ABCC2 | PM/IM vs NM/UM | 1.6 (-4.2, 7.3) | 0.60 | -1.0 (-2.1, -0.001) | 0.06 |
| SULT1A1 | PM/IM vs NM | 0.6 (-5.0, 6.3) | 0.83 | 0.9 (-0.09, 1.9) | 0.08 |
| UGT1A1 | PM/IM vs NM | 3.1 (-2.4, 8.6) | 0.27 | 0.3 (-0.9, 1.4) | 0.66 |
| CYP2B6 | PM/IM vs NM | -0.3 (-6.2, 5.6) | 0.93 | 0.4 (-0.6, 1.4) | 0.45 |
| SLCO1B1 | PM/IM vs NM | 0.4 (-5.1, 5.9) | 0.89 | 0.01 (-0.99, 1.0) | 0.99 |
| CYP2C8 | PM/IM vs NM | -3.4 (-9.6, 2.8) | 0.29 | -0.01 (-1.1, 1.1) | 0.98 |
| CYP2C9 | PM/IM vs NM | -8.1 (-13.7, -2.5) | 0.006 | 1.1 (0.08, 2.2) | 0.041 |
| CYP1A1 | PM/IM vs NM | 0.7 (-6.2, 7.5) | 0.84 | -0.6 (-1.9, 0.62) | 0.33 |
| CYP1A2 | PM/IM/NM vs UM | 2.5 (-6.6, 11.6) | 0.59 | -0.7 (-2.3, 0.9) | 0.40 |
| UGT2B17 | PM/IM vs NM | -4.7 (-9.8, 0.4) | 0.07 | -0.4 (-1.4, 0.5) | 0.41 |
| CYP2C19 | PM/IM vs NM/UM | -3.7 (-8.9, 1.6) | 0.18 | 0.01 (-0.97, 0.99) | 0.99 |
| CYP2A6 | PM/IM vs NM | 0.5 (-5.9, 6.9) | 0.87 | -0.7 (-1.9, 0.5) | 0.29 |
| VKORC1 | PM/IM vs NM | 0.8 (-4.9, 6.5) | 0.78 | -0.2 (-1.2, 0.8) | 0.71 |
| ABCG2 | PM/IM vs NM | -4.6 (-10.5, 1.4) | 0.14 | 0.4 (-0.7, 1.5) | 0.47 |
| UGT2B7 | PM vs IM/NM | -0.5 (-6.4, 5.5) | 0.88 | -0.3 (-1.3, 0.7) | 0.53 |
| SLC15A2 | PM vs IM/NM | -1.2 (-7.2, 4.7) | 0.69 | 0.4 (-0.7, 1.5) | 0.45 |
| SLC22A2 | PM/IM vs NM | -0.18 (-6.5, 6.1) | 0.96 | -0.7 (-1.7, 0.4) | 0.23 |
| SLC22A6 | PM/IM vs NM | -5.7 (-28.9, 17.6) | 0.63 | NA | NA |
| SLCO1B3 | PM vs IM/NM | -4.9 (-10.4, 0.69) | 0.09 | -0.2 (-1.2, 0.8) | 0.68 |
| TPMT | PM/IM vs NM | 0.02 (-8.4, 8.5) | 0.97 | -0.4 (-2.2, 1.4) | 0.65 |
| CYP2E1 | IM vs NM/UM | 0.84 (-4.7, 6.4) | 0.77 | -0.1 (-1.2, 0.9) | 0.79 |
| NAT1 | PM/IM vs NM | -2.9 (-13.8, 7.9) | 0.60 | -0.7 (-2.3, 0.9) | 0.39 |
| NAT2 | PM vs IM/NM | 1.3 (-4.1, 6.7) | 0.63 | -0.1 (-1.1, 0.9) | 0.86 |
| UGT2B15 | PM vs IM/NM | -5.2 (-10.9, 0.5) | 0.08 | 0.05 (-1.0, 1.1) | 0.93 |
| SLCO2B1 | PM/IM vs NM | -2.4 (-16.0, 11.2) | 0.73 | 0.7 (-1.7, 3.2) | 0.57 |
| SLC22A1 | PM/IM vs NM | -0.06 (-5.4, 5.3) | 0.98 | -0.5 (-1.5, 0.4) | 0.29 |
| GSTT2B | PM/IM vs NM | -3.4 (-8.8, 2.0) | 0.22 | -0.3 (-1.3, 0.7) | 0.55 |
| GSTT1 | PM/IM vs NM | -2.2 (-9.4, 4.9) | 0.54 | -0.3 (-1.4, 1.0) | 0.71 |
| GSTP1 | PM/IM vs NM | 0.5 (-5.4, 6.3) | 0.87 | 0.2 (-0.8, 1.2) | 0.74 |
| GSTM1 | PM/IM vs NM | -3.6 (-8.8, 1.6) | 0.18 | -0.03 (-1.0, 0.9) | 0.95 |
| DPYD | PM/IM vs NM | NA | NA | 0.2 (-3.2, 3.7) | 0.89 |
| CYP2D6 | PM/IM vs NM/UM | 1.2 (-4.1, 6.6) | 0.65 | 0.08 (-0.9, 1.1) | 0.88 |
| COMT | PM vs IM/NM | 0.24 (-5.2, 5.7) | 0.93 | -0.6 (-1.6, 0.3) | 0.20 |
| SLC28A7 rs16960359 | Variant carrier vs wild type | -2.1 (-4.8, 9.0) | 0.55 | – | – |
| ALPPL2 rs883013 | Variant carrier vs wild-type | 3.1 (-9.1, 2.9) | 0.31 | – | – |
–: Analysis not attempted because prior literature indicates the association is with anastrozole systemic concentrations.
†
Anastrozole analysis conducted in all patients with measured anastrozole systemic concentration.
Bold indicates p < 0.05.
IM: Intermediate metabolizer; NA: Analysis could not be conducted, since all patients had the same metabolizer phenotype; NM: Normal metabolizer; PM: Poor metabolizer; UM: Ultra-rapid metabolizer.