Table 2.
Association of CYP2D6 pharmacogenomics with tamoxifen outcomes.
| Studies | N | Alleles | DNA Source | Conclusions | Outcome | HR (95% CI) | P |
|---|---|---|---|---|---|---|---|
| Positive association | |||||||
| Goetz et al., 2005 [68] | 190 | *4 | PE-tissue, buccal swabs | *4/*4 patients had worse RFS and DFS | RFS DFS |
2.71 (1.15–6.41) 2.44 (1.22–4.90) |
0.023 0.012 |
| Schroth et al., 2007 [69] | 206 | *4, *5, *10, *41, CNV | normal breast tissue | Decreased function alleles (*4, *5, *10 and *41) were associated with higher rates of recurrence and shorter relapse free periods | RFS EFS |
2.24 (1.16–4.33) 1.89 (1.10–3.25) |
0.02 0.02 |
| Ramón et al., 2010 [70] | 91 | 33 alleles | blood | Patients with *4/*4, *4/*41, *1/*5 or *2/*5 genotypes had shorter DFS | 0.016 | ||
| Lammers et al., 2010 [71] | 99 | *3, *4, *5, *6, *10, *41 | blood | PMs had worse overall survival compared to NMs | OS | 2.09 (1.06–4.12) | 0.034 |
| Schroth et al., 2009 [72] | 1325 | *3,*4, *5, *10, *41 | blood, fresh frozen or PE-tissue | Decreased activity (NM/IM; PM) had worse EFS and DFS | EFS DFS |
1.35 (1.08–1.68) 1.31 (1.06–1.61) |
0.007 0.02 |
| Goetz et al., 2013 [73] | 453 | *3, *4, *6, *10, *41 | PE- tissue | PM/PM patients had higher risk of disease event compared to NM/NM patients | OR | 2.45 (1.05–5.73 | 0.04 |
| Damodaran et al., 2012 [74] | 132 | *1, *2, *4, *5, *10 | blood | CYP2D6 activity scores <0.5 had worse RFS compared to activity scores >1 | RFS | 7.29 (2.92–18.2) | <0.001 |
| Saladores et al., 2015 [75] | 587 | *3, *4, *5, *6, *9, *10, *41, CNV | blood | Improved DRFS was associated with increased CYP2D6 activity score | DRFS | 0.62 (0.43–0.9) | 0.013 |
| Xu et al., 2008 [76] | 152 | *10 | blood, fresh frozen or PE-tissue | *10/*10 was associated with worse DFS | DFS | 4.7 (1.1–20.0) | 0.04 |
| Kiyotani et al., 2008 [77] | 67 | *4, *5, *6, *10, *14, *18, *21, *41 | blood | *10/*10 genotype had worse RFS | RFS | 10.04 (1.17–86.3) | 0.036 |
| Kiyotani et al., 2010 [78] | 282 | *4, *5, *6, *10, *14B, *18, *21, *36, *41, CNV | blood | Presence of two variant alleles was associated with worse RFS compared to patients with no variants | RFS | 9.52 (2.79–32.45) | <0.0001 |
| Negative association | |||||||
| Rae et al., 2012 [80] | 588 | *2, *3, *4, *6, *10, *41 | PE-tissue | PMs did not have reduced recurrence rates compared to NMs | RFS | 0.99 (0.48–2.08) | 0.99 |
| Regan et al., 2012 [81] | 973 | *2, *3, *4, *5, *6, *7, *10, *17, *41 | PE-tissue | IMs and PMs treated with tamoxifen monotherapy were not associated with BCFI | BCFI | 0.86 (0.6–1.24) | 0.35 |
| Abraham et al., 2010 [82] | 3155 | *4, *5, *6, *9, *10, *41, CNV | blood | PM/IM patients did not have reduced survival outcomes compared to NMs | BCSS | 0.93 (0.55–1.57) | 0.78 |
| Nowell et al., 2005 [83] | 160 | *3, *4, *6 | PE-tissue | *4/*4, *1/*4 were not associated with reduced DFS compared to *1/*1 | DFS | 0.67 (0.33–1.35) | 0.19 |
| Park et al., 2012 [84] | 716 | *2, *5, *10, *41 | blood | Homozygous variant carriers did not have reduced RFS | RFS | 1.14 (0.68–1.92) | 0.61 |
| Hertz et al., 2017 [86] | 476 | *2, *3, *4, *6, *10, *41, CNV | Fresh frozen tumors | CYP2D6 activity score was not associated with RFS | RFS | 1.16 (0.84–1.62) | 0.37 |
| Kiyotani et al., 2010 [87] | 167 | *1, *4, *5, *10, *21, *36, *41 | blood | No association between genotype and RFS in patients on tamoxifen-combined therapy | RFS | 0.64 (0.20–1.99) | 0.44 |
HR, Hazard ratio; CI, confidence interval; PE, paraffin-embedded; RFS, recurrence free survival; DFS, disease free survival; CNV, copy number variation; EFS, event free survival; NM, CYP2D6 normal metabolizer; OS, overall survival; IM, CYP2D6 intermediate metabolizer; PM, CYP2D6 poor metabolizer; DRFS, distant relapse free survival; BCFI, breast cancer-free interval; BCSS, breast cancer specific survival.